By default PowerPoint or Excel 2007 will create multicolored pie charts or single-colored bar charts.
When you create a bar chart in Excel or PowerPoint 2007, the software defaults to a single-color chart. However, it’s not always the case that the biggest or smallest data point is the emphasis of your chart. Using a contrasting color on a specific data point will naturally draw attention to a particular area of the chart.
Select the data element that you want to highlight and then use the fill color feature to change its color. If you stick with the default setting for pie charts, all of the pie slices receive a different color, which makes it more difficult to isolate a particular part of the pie chart. Following a similar approach to the bar charts, it might be helpful to add a second color to a one-color style pie chart so that you can highlight the specific slice of the pie chart that you’d like to emphasize in your PowerPoint presentation. In PPT 2003, you could actually break apart (ungroup) charts more easily so you could actually animate them more easily. You can still achieve the same effect in PPT 2007 with some work, but unfortunately it is no where as easy as it was in PPT 2003. You could also do a multicolored pie chart where all of the colors were muted or dulled down except for the one data point you want to emphasize.
Once you have visualized the slides for a PowerPoint presentation, you can start to write notes and attach files to each branch i.e. Although a mind map is created none linearly, in MindView there is an order of which the branches are exported to PowerPoint. Templates can easily be customized in the export wizard, where you can select things such as; including an image of the mind map as a slide and exclusion of certain contents. The attached objects can also be controlled under the attached Object tab in the export Wizard, where for instance you can determine if you want a video attached in the mind map to be embedded within the respective slide or shown as a hyperlink. Importing a PowerPoint file as a mind map gives you a way to view the presentation in a more non-linier way and provides a unique overview. For many years, researchers have been seeking to understand the body's ability to repair and replace the cells and tissues of some organs, but not others. Unlike embryonic stem cells, which are defined by their origin (the inner cell mass of the blastocyst), adult stem cells share no such definitive means of characterization.
In order to be classified as an adult stem cell, the cell should be capable of self-renewal for the lifetime of the organism. An adult stem cell should also be able to give rise to fully differentiated cells that have mature phenotypes, are fully integrated into the tissue, and are capable of specialized functions that are appropriate for the tissue. The majority of researchers who lay claim to having identified adult stem cells rely on two of these characteristics—appropriate cell morphology, and the demonstration that the resulting, differentiated cell types display surface markers that identify them as belonging to the tissue. It is often difficult—if not impossible—to distinguish adult, tissue-specific stem cells from progenitor cells, which are found in fetal or adult tissues and are partly differentiated cells that divide and give rise to differentiated cells. It was not until recently that anyone seriously considered the possibility that stem cells in adult tissues could generate the specialized cell types of another type of tissue from which they normally reside—either a tissue derived from the same embryonic germ layer or from a different germ layer (see Table 1.1. The term plasticity, as used in this report, means that a stem cell from one adult tissue can generate the differentiated cell types of another tissue.
To be able to claim that adult stem cells demonstrate plasticity, it is first important to show that a cell population exists in the starting tissue that has the identifying features of stem cells. To show that the adult stem cells can generate other cell types requires them to be tracked in their new environment, whether it is in vitro or in vivo. In the experiments reported to date, adult stem cells may assume the characteristics of cells that have developed from the same primary germ layer or a different germ layer (see Figure 4.2.
Alternatively, adult stem cells may differentiate into a tissue that—during normal embryonic development—would arise from a different germ layer. To study plasticity of stem cells derived from the brain, the researcher must overcome several problems.
The differentiated cell types that result from plasticity are usually reported to have the morphological characteristics of the differentiated cells and to display their characteristic surface markers.
More than 30 years ago, Altman and Das showed that two regions of the postnatal rat brain, the hippocampus and the olfactory bulb, contain dividing cells that become neurons [5, 6]. Today, scientists believe that stem cells in the fetal and adult brain divide and give rise to more stem cells or to several types of precursor cells. A second group of adult CNS stem cells, described in mice but not in humans, occurs in a streak of tissue that connects the lateral ventricle and the olfactory bulb, which receives odor signals from the nose. A recent report indicates that the astrocytes that occur in the subventricular zone of the rodent brain act as neural stem cells.
A series of similar in vitro studies based on the formation of neurospheres was used to identify the subependymal zone as a source of adult rodent CNS stem cells.
To show that Dil+ cells were neural stem cells and could generate astrocytes and oligodendrocytes as well as neurons, a neurosphere assay was performed in vitro. To show that ependymal cells can also divide in vivo, bromodeoxyuridine (BrdU) was administered in the drinking water to rats for a 2- to 6-week period.
Collectively, the data suggest that CNS ependymal cells in adult rodents can function as stem cells.
In the human dentate gyrus, some BrdU-labeled cells express NeuN, neuron-specific enolase, or calbindin, all of which are neuronal markers. It may seem obvious that the fetal brain contains stem cells that can generate all the types of neurons in the brain as well as astrocytes and oligodendrocytes, but it was not until fairly recently that the concept was proven experimentally.
Neural stem cells in the mammalian fetal brain are concentrated in seven major areas: olfactory bulb, ependymal (ventricular) zone of the lateral ventricles (which lie in the forebrain), subventricular zone (next to the ependymal zone), hippocampus, spinal cord, cerebellum (part of the hindbrain), and the cerebral cortex.
In a 1999 study, a serum-free growth medium that included EGF and FGF2 was devised to grow the human fetal CNS stem cells. Thus, neural crest cells migrate far more extensively than other fetal neural stem cells during development, form mesenchymal tissues, most of which develop from embryonic mesoderm as well as the components of the CNS and PNS which arises from embryonic ectoderm. Recent studies indicate that neural crest cells persist late into gestation and can be isolated from E14.5 rat sciatic nerve, a peripheral nerve in the hindlimb. Two more apparent stem cell types have been reported in circulating blood, but have not been shown to originate from the bone marrow.
HSCs can reconstitute the hematopoietic system of mice that have been subjected to lethal doses of radiation to destroy their own hematopoietic systems.
Over the years, many combinations of surface markers have been used to identify, isolate, and purify HSCs derived from bone marrow and blood.
Short-term HSCs differentiate into lymphoid and myeloid precursors, the two classes of precursors for the two major lineages of blood cells. Attempts to induce HSC to proliferate in vitro—on many substrates, including those intended to mimic conditions in the stroma—have frustrated scientists for many years.
Also important to HSC proliferation and differentiation are interactions of the cells with adhesion molecules in the extracellular matrix of the bone marrow stroma [83, 101, 110]. To date, it has not been possible to isolate a population of pure stromal cells from bone marrow.
It is often difficult—if not impossible—to distinguish adult, tissue-specific stem cells from progenitor cells. Evidence that hemangioblasts do exist comes from studies of mouse embryonic stem cells that are directed to differentiate in vitro. Several recent reports indicate that the bone marrow contains cells that can give rise to new blood vessels in tissues that are ischemic (damaged due to the deprivation of blood and oxygen) [8, 29, 49, 94]. In more recent experiments, human bone marrow-derived cells were injected into the tail veins of rats with induced cardiac ischemia.
And, in a series of experiments in adult mammals, progenitor endothelial cells were isolated from peripheral blood (of mice and humans) by using antibodies against CD34 and Flk-1, the receptor for VEGF.
Satellite cells in skeletal muscle were identified 40 years ago in frogs by electron microscopy [62], and thereafter in mammals [84]. Another report indicates that a different kind of stem cell, called an SP cell, can also regenerate skeletal muscle may be present in muscle and bone marrow. The skin of mammals contains at least three populations of epithelial cells: epidermal cells, hair follicle cells, and glandular epithelial cells, such as those that make up the sweat glands. The identity of stem cells that can repopulate the liver of adult mammals is also in question. Adult stem cells can proliferate without differentiating for a long period (a characteristic referred to as long-term self-renewal), and they can give rise to mature cell types that have characteristic shapes and specialized functions. Some adult stem cells have the capability to differentiate into tissues other than the ones from which they originated; this is referred to as plasticity. To date, published scientific literature indicates that adult stem cells have been derived from brain, bone marrow, peripheral blood, dental pulp, spinal cord, blood vessels, skeletal muscle, epithelia of the skin and digestive system, cornea, retina, liver, and pancreas; thus, adult stem cells have been found in tissues that develop from all three embryonic germ layers.
Hematopoietic stem cells from bone marrow are the most studied and used for clinical applications in restoring various blood and immune components to the bone marrow via transplantation. Several populations of adult stem cells have been identified in the brain, particularly the hippocampus. There are now several reports of adult stem cells in other tissues (muscle, blood, and fat) that demonstrate plasticity. Rarely have experiments that claim plasticity demonstrated that the adult stem cells have generated mature, fully functional cells or that the cells have restored lost function in vivo. Is it possible to manipulate adult stem cells to increase their ability to proliferate in vitro, so that adult stem cells can be used as a sufficient source of tissue for transplants?
What is the best evidence that adult stem cells show plasticity and generate cell types of other tissues? Is it possible to manipulate adult stem cells to increase their ability to proliferate in vitro so that adult stem cells can be used as a sufficient source of tissue for transplants? At a workshop recently I heard someone giving a talk which was really interesting and I took away some valuable points from it.
So from my experience of both creating and listening to presentations, I’ve put together some tips of what I think can make or break a presentation. Put your company branding and logo on the presentation to make it look professional and help build a relationship with your brand and the audience. Keep animations and transitions to a minimum so they don’t confuse and distract the audience.
Use creative ways of presenting your information eg, pictures, charts, and animations which will grab people’s attention.
Don’t wander off the subject, and if you do, ensure the audience knows why and quickly come back to it. Read from a script – it can sound stilted and prevents you from making eye contact with the audience.
Valerie Eaton is the owner of Smart VA Ltd, providers of virtual assistant support to small businesses and self-employed professionals.
MatchWare MindView's brainstorming mode is an invaluable tool for capturing the bursts of inspiration that emerge during group planning meetings. MatchWare MindView's Multimedia Catalog contains 1500 high quality clipart illustrations created specifically for business and education use, as well as numerous root shapes and map styles.
MindView 5 Business Edition allows you to add numeric values to the branches of your Mind Map, for example sales numbers, costs, exchange rates and so on, and also formulas to carry out calculations on the values. To enter values, you use the Calculation panel, conveniently accessed from a tab on the right of the workspace.Values appear on the Mind Map under the branch labels. In addition to text notes, MatchWare MindView lets you attach any number of external resources to the branches of your map, including documents, pictures, videos, sounds, hyperlinks, Flash® animations and more. MatchWare MindView includes over 80 business and educational templates, supported by over one thousand high quality clipart images.
MatchWare MindView lets you link several documents by creating connections between relevant branches. MatchWare MindView lets you develop your Mind Map in 6 different views depending on the nature of your data. The Mind Map view represents the map with the root in the center and the main branches radiating from it in a clockwise direction. This shows your map as a hierarchical pyramid, with the root at the top, the main branches underneath, the sub-branches below the main branches, and so on. This view represents your map as a sequential list of topics placed either on the right or left of the root (Right view or Left view). Use this view to represent your map as a linear hierarchical list, which you can expand and collapse as required.
Use the Timeline view to display events such as company history, execution of marketing strategies, project plans and historical data.
The MatchWare MindView Gantt view, specific to the Business Edition, is a specialized view dedicated to the creation, editing and management of project plans according to the rules of project management.
MatchWare MindView lets you add task information to the branches of your Mind Maps in order to create simple task lists or complete projects of interrelated tasks.
As mentioned above, MatchWare MindView Business Edition lets you export your task lists to the task folder of your choice in Microsoft Outlook. Start by brainstorming your tasks, then allocate resources and establish priorities using the intuitive Mind Map interface.
Start by storyboarding your presentation in the Mind Map view and then export it to PowerPoint to create an engaging and professional-looking presentation based on one of MindView's ready-made templates. As with Word, you can re-import your presentation into MindView at any time, including slides, pictures and comments you might have added.
With MindView 5 Business Edition you can export your Mind Map as a Microsoft® Excel spreadsheet. When exporting, you can choose from several professionally designed templates to enhance the look of the spreadsheet. Not only are all the calculation values exported, but if you use the Advanced Export option, you can also export any or all of the standard task data fields, namely Start, End, Duration, Completion, Priority and Resources. After working in Excel you can re-import the spreadsheet back into MindView to obtain an updated Mind Map containing all the data changes you made in Excel. MatchWare MindView Business Edition lets you create, refine and manage project plans from start to finish in its dedicated, dynamic Gantt view.
Conversely, you can import existing Microsoft Project plans into the Gantt view directly from Microsoft Project or via Microsoft Project's XML format. Create professional quality websites based on your Mind Map with a single click - No HTML experience required!
You can also re-import your Mediator presentation into MindView, including any pages added in Mediator.
The Pack & Email feature lets you distribute your maps to others, including all multimedia content and external linked files.
Unfortunately, these default color combinations can cause charts to communicate less effectively unless they are modified.
The software has no way of knowing which particular data point is the main focus of your graph or chart.
With a one-color approach, your audience cannot quickly understand the emphasis of your chart.
You end up having to highlight part of the chart with a circle or arrow to draw your audience’s attention to a key data point on the chart.
In order to alter a chart’s colors, you left-click on the chart so that all of the elements of the chart are highlighted. I think with bar charts another way I think works quite well is by introducing the non-central bars first, and then by way of custom animation bringing in the relevant point.
In PPT 2007, either all of the chart or parts of the chart end up as bitmap images which you can’t break apart. If you’re looking to move from PowerPoint apprentice to ninja, subscribe to this RSS today!
MindView is a professional mind mapping tool with a powerful MS Office integration that enables you to export and import a mind map to PowerPoint. For a more clear understanding of the connection between the mind map branches and the PowerPoint slides, you can apply a numbering schema to the branches within MindView. The export order of the mind map goes clock wise starting from the upper right corner of the mind map.
First you are able to select between different PowerPoint templates, styles and formatting. When converting a mind map to PowerPoint, it can be tricky with the last level of branches in the mind map.
The heading of the slide becomes the branch text, whereas other text will be inserted as a text note and pictures, videos, etc. After years of work pursuing the how and why of seemingly indiscriminant cell repair mechanisms, scientists have now focused their attention on adult stem cells. First, they can make identical copies of themselves for long periods of time; this ability to proliferate is referred to as long-term self-renewal. Their primary functions are to maintain the steady state functioning of a cell—called homeostasis—and, with limitations, to replace cells that die because of injury or disease [44, 58]. This criterion, although fundamental to the nature of a stem cell, is difficult to prove in vivo.
In other words, a single adult stem cell should be able to generate a line of genetically identical cells, which then gives rise to all the appropriate, differentiated cell types of the tissue in which it resides. Some studies demonstrate that the differentiated cells that are derived from adult stem cells are truly functional, and a few studies show that cells are integrated into the differentiated tissue in vivo and that they interact appropriately with neighboring cells. In general, three methods are used to determine whether candidate adult stem cells give rise to specialized cells. These are cells found in many organs that are generally thought to be present to replace cells and maintain the integrity of the tissue. At this time, there is no formally accepted name for this phenomenon in the scientific literature.
Then, it is necessary to show that the adult stem cells give rise to cell types that normally occur in a different tissue. In general, this has been accomplished by obtaining the stem cells from a mouse that has been genetically engineered to express a molecular tag in all its cells.
For example, bone marrow-derived cells may differentiate into neural tissue, which is derived from embryonic ectoderm [15, 65]. The vast majority of experiments on plasticity have been conducted with adult stem cells derived either from the bone marrow or the brain. Stem cells from the central nervous system (CNS), unlike bone marrow cells, do not occur in a single, accessible location. In reports that transplanted adult stem cells show plasticity in vivo, the stem cells typically are shown to have integrated into a mature host tissue and assumed at least some of its characteristics [15, 28, 51, 65, 71]. Despite these reports, the prevailing view at the time was that nerve cells in the adult brain do not divide. Neuronal precursors (also called neuroblasts) divide and give rise to nerve cells (neurons), of which there are many types.
All occur in the adult rodent brain and preliminary evidence indicates they also occur in the adult human brain. In rodents, olfactory bulb neurons are constantly being replenished via this pathway [59, 61]. CNS stem cells found in the forebrain that surrounds the lateral ventricles are heterogeneous and can be distinguished morphologically. The cells with astrocyte markers appear to generate neurons in vivo, as identified by their expression of specific neuronal markers. In these experiments, single, candidate stem cells derived from the subependymal zone are induced to give rise to neurospheres in the presence of mitogens—either epidermal growth factor (EGF) or fibroblast growth factor-2 (FGF-2).
Another group of potential CNS stem cells in the adult rodent brain may consist of the ependymal cells themselves [47]. Dil-labeled cells were dissociated from the ventricular system and cultured in the presence of mitogen to generate neurospheres.
These studies and other leave open the question of whether cells that directly line the ventricles—those in the ventricular zone—or cells that are at least a layer removed from this zone—in the subventricular zone are the same population of CNS stem cells.
The hippocampus is one of the oldest parts of the cerebral cortex, in evolutionary terms, and is thought to play an important role in certain forms of memory. The labeled neuron-like cells resemble dentate gyrus granule cells, in terms of their morphology (as they did in mice). Not surprisingly, fetal stem cells are numerous in fetal tissues, where they are assumed to play an important role in the expansion and differentiation of all tissues of the developing organism.
There has been a long-standing question as to whether or not the same cell type gives rise to both neurons and glia.
In one study, however, investigators derived clonal cell lines from CNS stem cells isolated from the diencephalon and cortex of human fetuses, 10.5 weeks post-conception [103]. Although most of the cells died, occasionally, single CNS stem cells survived, divided, and ultimately formed neurospheres after one to two weeks in culture.
This close link, in neural crest development, between ectodermally derived tissues and mesodermally derived tissues accounts in part for the interest in neural crest cells as a kind of stem cell. One population of bone marrow cells, the hematopoietic stem cells (HSCs), is responsible for forming all of the types of blood cells in the body. One population, called pericytes, may be closely related to bone marrow stromal cells, although their origin remains elusive [12]. Of all the cell types in the body, those that survive for the shortest period of time are blood cells and certain kinds of epithelial cells.


This test, the rescue of lethally irradiated mice, has become a standard by which other candidate stem cells are measured because it shows, without question, that HSCs can regenerate an entire tissue system—in this case, the blood [9, 99]. Although HSCs proliferate readily in vivo, they usually differentiate or die in vitro [26].
Bone marrow (BM) stromal cells have long been recognized for playing an important role in the differentiation of mature blood cells from HSCs (see Figure 4.3. Panels of markers used to identify the cells include receptors for certain cytokines (interleukin-1, 3, 4, 6, and 7) receptors for proteins in the extracellular matrix, (ICAM-1 and 2, VCAM-1, the alpha-1, 2, and 3 integrins, and the beta-1, 2, 3 and 4 integrins), etc. Bone marrow adipocytes and myelosupportive stromal cells—both of which are derived from BM stromal cells—may be regarded as interchangeable phenotypes [10, 11]. With that caveat in mind, the following summary identifies reports of stem cells in various adult tissues. Endothelial cells line the inner surfaces of blood vessels throughout the body, and it has been difficult to identify specific endothelial stem cells in either the embryonic or the adult mammal. These studies have shown that a precursor cell derived from mouse ES cells that express Flk-1 [the receptor for vascular endothelial growth factor (VEGF) in mice] can give rise to both blood cells and blood vessel cells [88, 109]. But it is unclear from these studies what cell type(s) in the bone marrow induced angiogenesis. The human cells migrated to the rat heart where they generated new blood vessels in the infarcted muscle (a process akin to vasculogenesis), and also induced angiogenesis. The cells were mononuclear blood cells (meaning they have a nucleus) and are referred to as MBCD34+ cells and MBFlk1+ cells. Skeletal muscle, like the cardiac muscle of the heart and the smooth muscle in the walls of blood vessels, the digestive system, and the respiratory system, is derived from embryonic mesoderm. Satellite cells occur on the surface of the basal lamina of a mature muscle cell, or myofiber. Are skeletal muscle satellite cells true adult stem cells or are they instead precursor cells? SP stands for a side population of cells that can be separated by fluorescence-activated cell sorting analysis.
Epithelial cells, which constitute 60 percent of the differentiated cells in the body are responsible for covering the internal and external surfaces of the body, including the lining of vessels and other cavities.
The replacement patterns for epithelial cells in these three compartments differ, and in all the compartments, a stem cell population has been postulated. These stem cells proliferate in the basal region, and then differentiate as they move toward the outer surface of the skin.
Recent studies in rodents indicate that HSCs (derived from mesoderm) may be able to home to liver after it is damaged, and demonstrate plasticity in becoming into hepatocytes (usually derived from endoderm) [54, 77, 97]. There are at least two other populations of adult stem cells that have been identified from bone marrow and blood.
Very few published research reports on plasticity of adult stem cells have, however, included clonality studies.
Evidence is accumulating that, although they occur in small numbers, adult stem cells are present in many differentiated tissues. An emerging concept is that, in adult mammals, there may be a population of "universal" stem cells. However, it’s important to remember that a clearly delivered and well-designed presentation will promote you and your business professionally and effectively to your audience. This intelligent piece of software makes it easy to create projects, reports and timelines or simply to organize general work. This powerful, yet easy-to-use program lets you instantly capture those ideas without disrupting the brainstorming process to define their precise wording or positioning. Simply use the keyword-based search tool to find the elements you need and drop them onto your workspace. Built-in functions allow you to display values automatically rolled up from lower sub-branches to higher ones. Hyperlinks can be used to connect to websites, folders, or files such as Excel or PDF documents.
Once you have created your Mind Map using one of these templates, you can easily tailor it to meet your specific needs. Clicking the branch connection from the source document automatically opens the linked map in the target document.
This view works especially well in the brainstorming mode, when you want to collect ideas related to your theme without worrying about analyzing or organizing them at that stage.
The Outline view allows easy navigation through the document from top to bottom and provides another tool for brainstorming. Simply insert dates or times on your branches and switch to the Timeline view to see your information displayed along a horizontal time axis. A special task panel lets you add data such as start and end dates, resources, priority and completion levels to any branch during initial brainstorming or at any point in the project planning process. You can also import task lists from Microsoft Outlook and use MindView to synchronize the two versions of your task list stored in Outlook and in MindView.
At that stage, switch to the Gantt view to fine-tune your project planning using the popular Gantt chart interface and take advantage of all of the standard project management features. Conversely, you can import project plans developed in Microsoft® Project into MindView to make full use of MindView's innovative brainstorming features. Then export to Word using our professional, ready-to-use templates to produce a fully formatted Word document, complete with table of contents, page numbers, headers and footers, and a structure that reflects the precise structure of your Mind Map (main branches become main paragraphs, sub-branches become sub-paragraphs, and so on). You can for instance create a Mind Map to brainstorm a budget forecast, consolidate it by using the Calculation panel to enter the actual sales figures, and then export the map as an Excel spreadsheet to perform a more detailed analysis of your figures in Excel. You can also determine how the branch layout should be represented in the spreadsheet, by choosing to export the map either as a structured list reflecting the branch hierarchy, or as a numbered list where each sequence number identifies the position of the branch in the overall map.
You can also import task lists from Microsoft Outlook and use MindView to synchronize the versions of the task list stored in Outlook and in MindView.
You can also export your project plans to Microsoft Project for further expansion, if necessary, either directly in Microsoft Project's .mpp format or via Microsoft Project's XML format. This is particularly useful if you want to review the structure of your plans using the Mind Mapping technique or view your plans as timelines. MatchWare MindView comes with a host of professional HTML export templates offering different navigation options, such as tree view, level list or easily customizable standard links and buttons.
These options are particularly useful if you do not have the related software application installed on your computer. You can copy the entire map to a specific folder, compress it as a zip file or compress it as a single MindView file. After installing the viewer, anyone can view your Mind Maps in any of the MindView views, including the Timeline view and the Gantt view, filter them and print them. Alternatively, you may have to physically point or scribble on the part of the chart during your presentation. The chart on the right has been altered so that it naturally draws your audience's eyes to a key data point on your chart.
Notice that MindView enables you to attach an unlimited number of files to each branch and supports all file formats.
By dragging and dropping branches in a different order in the mind map, you are able to rearrange branches i.e.
These will often be viewed as bullet points on the prior slide and not as individual branches.
Of course once in PowerPoint you can change everything, but you will have the structure and contents from MindView premade. It has long been known that stem cells are capable of renewing themselves and that they can generate multiple cell types. Second, they can give rise to mature cell types that have characteristic morphologies (shapes) and specialized functions. A stem cell is an unspecialized cell that is capable of replicating or self renewing itself and developing into specialized cells of a variety of cell types.
For example, only an estimated 1 in 10,000 to 15,000 cells in the bone marrow is a hematopoietic (bloodforming) stem cell (HSC) [105]. Some have proposed that stem cells are somehow set aside during fetal development and restrained from differentiating.
It is nearly impossible, in an organism as complex as a human, to design an experiment that will allow the fate of candidate adult stem cells to be identified in vivo and tracked over an individual's entire lifetime. Again, this property is difficult to demonstrate in vivo; in practice, scientists show either that a stem cell is clonogenic in vitro, or that a purified population of candidate stem cells can repopulate the tissue. At present, there is, however, a paucity of research, with a few notable exceptions, in which researchers were able to conduct studies of genetically identical (clonal) stem cells. Progenitor cells give rise to certain types of cells—such as the blood cells known as T lymphocytes, B lymphocytes, and natural killer cells—but are not thought to be capable of developing into all the cell types of a tissue and as such are not truly stem cells. For example, studies have shown that blood stem cells (derived from mesoderm) may be able to generate both skeletal muscle (also derived from mesoderm) and neurons (derived from ectoderm). It is variously referred to as "plasticity" [15, 52], "unorthodox differentiation" [10] or "transdifferentiation" [7, 54]. It is then necessary to show that the labeled adult stem cells have adopted key structural and biochemical characteristics of the new tissue they are claimed to have generated. For example, many plasticity experiments involve stem cells derived from bone marrow, which is a mesodermal derivative. And—reciprocally—neural stem cell lines cultured from adult brain tissue may differentiate to form hematopoietic cells [13], or even give rise to many different cell types in a chimeric embryo [17].
The bone marrow-derived cells are sometimes sorted—using a panel of surface markers—into populations of hematopoietic stem cells or bone marrow stromal cells [46, 54, 71]. Instead, they are scattered in three places, at least in rodent brain—the tissue around the lateral ventricles in the forebrain, a migratory pathway for the cells that leads from the ventricles to the olfactory bulbs, and the hippocampus.
Many plasticity experiments involve injury to a particular tissue, which is intended to model a particular human disease or injury [13, 54, 71]. Also, it is not yet clear to what extent plasticity can occur in experimental settings, and how—or whether—the phenomenon can be harnessed to generate tissues that may be useful for therapeutic transplantation. In fact, the notion that stem cells in the adult brain can generate its three major cell types—astrocytes and oligodendrocytes, as well as neurons—was not accepted until far more recently. One group occupies the brain tissue next to the ventricles, regions known as the ventricular zone and the sub-ventricular zone (see discussion below). A third possible location for stem cells in adult mouse and human brain occurs in the hippocampus, a part of the brain thought to play a role in the formation of certain kinds of memory [27, 34]. The in vitro assay to demonstrate that these astrocytes are, in fact, stem cells involves their ability to form neurospheres—groupings of undifferentiated cells that can be dissociated and coaxed to differentiate into neurons or glial cells [25]. Most of the neurospheres were Dil+; they could self-renew and generate neurons, astrocytes, and oligodendrocytes when induced to differentiate. Through a series of experiments, it was shown that ependymal cells divide slowly in vivo and give rise to a population of progenitor cells in the subventricular zone [47]. Many of the CNS ependymal cells are not actively dividing (quiescent), but they can be stimulated to do so in vitro (with mitogens) or in vivo (in response to injury). A new study, based on the finding that they express different genes, confirms earlier reports that the ventricular and subventricular zone cell populations are distinct. The region of the hippocampus in which stem cells apparently exist in mouse and human brains is the subgranular zone of the dentate gyrus. Other BrdU-labeled cells express glial fibrillary acidic protein (GFAP) an astrocyte marker. Depending on the developmental stage of an animal, fetal stem cells and precursor cells—which arise from stem cells—may make up the bulk of a tissue.
In studies of the developing rodent brain, it has now been shown that all the major cell types in the fetal brain arise from a common population of progenitor cells [20, 34, 48, 80, 108]. These cells appear to represent different stem cell populations, rather than a single population of stem cells that is dispersed in multiple sites. The study is unusual, not only because it involves human CNS stem cells obtained from fetal tissue, but also because the cells were used to generate clonal cell lines of CNS stem cells that generated neurons, astrocytes, and oligodendrocytes, as determined on the basis of expressed markers. During fetal development, neural crest cells migrate from the sides of the neural tube as it closes. When transplanted into chick embryos, the rat neural crest cells develop into neurons and glia, an indication of their stem cell-like properties [67]. The second population of blood-born stem cells, which occur in four species of animals tested—guinea pigs, mice, rabbits, and humans—resemble stromal cells in that they can generate bone and fat [53].
For example, red blood cells (erythrocytes), which lack a nucleus, live for approximately 120 days in the bloodstream. HSCs were first proven to be blood-forming stem cells in a series of experiments in mice; similar blood-forming stem cells occur in humans. In young adult mice, an estimated 8 to 10 % of long-term HSCs enter the cell cycle and divide each day.
The mechanisms and pathways that lead to their differentiation are still being investigated [1, 2].
Thus, much of the research on HSCs has been focused on understanding the factors, cell-cell interactions, and cell-matrix interactions that control their proliferation and differentiation in vivo, with the hope that similar conditions could be replicated in vitro. When bone marrow is dissociated, and the mixture of cells it contains is plated at low density, the stromal cells adhere to the surface of the culture dish, and the HSCs do not. Adipocytes do not develop until postnatal life, as the bones enlarge and the marrow space increases to accommodate enhanced hematopoiesis. During embryonic development, just after gastrulation, a kind of cell called the hemangioblast, which is derived from mesoderm, is presumed to be the precursor of both the hematopoietic and endothelial cell lineages. Both VEGF and fibroblast growth factor-2 (FGF-2) play critical roles in endothelial cell differentiation in vivo [79]. In a study which sought to address that question, researchers found that adult human bone marrow contains cells that resemble embryonic hemangioblasts, and may therefore be called endothelial stem cells. The candidate endothelial stem cells are CD34+(a marker for HSCs), and they express the transcription factor GATA-2 [51]. When plated in tissue-culture dishes, the cells attached to the substrate, became spindle-shaped, and formed tube-like structures that resemble blood vessels.
To date, at least three populations of skeletal muscle stem cells have been identified: satellite cells, cells in the wall of the dorsal aorta, and so-called "side population" cells. Intravenously injecting these muscle-derived stem cells restored the expression of dystrophin in mdx mice. For example, stem cells in the bulge region of the hair follicle appear to give rise to multiple cell types. But the question remains as to whether cells from the bone marrow normally generate hepatocytes in vivo. Current methods for characterizing adult stem cells are dependent on determining cell surface markers and observations about their differentiation patterns in test tubes and culture dishes.
Proliferation and differentiation of brain stem cells are influenced by various growth factors. That is, there is limited evidence that a single adult stem cell or genetically identical line of adult stem cells demonstrates plasticity. And if the latter is true—which seems to be the case—exactly how do adult stem cells arise, and why do they remain in an undifferentiated state, when all the cells around them have differentiated?
What are the signals that regulate the proliferation and differentiation of stem cells that demonstrate plasticity?
Cytological demonstration of the clonal nature of spleen colonies derived from transplanted mouse marrow cells.
Multipotential cells in the bone marrow stroma: regulation in the context of organ physiology. Growth kinetics, self-renewal, and the osteogenic potential of purified human mesenchymal stem cells during extensive subcultivation and following cryopreservation. Skeletal myogenic progenitors originating from embryonic dorsal aorta coexpress endothelial and myogenic markers and contribute to postnatal muscle growth and regeneration.
Once all the ideas are collected, simply click and drag the branches and sub-branches to move them to the appropriate position. If for instance you want to create a Mind Map to consolidate the sales figures coming from different geographical regions, you can use the built in function SUM to add up values entered on the outermost sub-branches (the regions), providing a grand total on the root and sub-totals on intermediate branches. All these attached resources are easily viewed by simply clicking their names in the object list associated with the branch. Ideas and suggestions for expansion are provided in various notes and pop-up comments.To help you get started, MatchWare MindView Business Edition also includes many ready-made project plans for common business activities, such as organizing a tradeshow, producing a publication, launching a product, etc. You can also detach a branch to create a second Mind Map in the same workspace or in a new document.
It is also a convenient method of entering and viewing task information related to the branches of your map (see Task Management below).
The different timescales available (standard, daily, weekly, historic and geological) let you represent a variety of time-related events.
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Today, there is new evidence that stem cells are present in far more tissues and organs than once thought and that these cells are capable of developing into more kinds of cells than previously imagined. Typically, stem cells generate an intermediate cell type or types before they achieve their fully differentiated state. The product of a stem cell undergoing division is at least one additional stem cell that has the same capabilities of the originating cell. Furthermore, adult stem cells are dispersed in tissues throughout the mature animal and behave very differently, depending on their local environment.
Definitions of adult stem cells vary in the scientific literature range from a simple description of the cells to a rigorous set of experimental criteria that must be met before characterizing a particular cell as an adult stem cell.
In order to fully characterize the regenerating and self-renewal capabilities of the adult stem cell, and therefore to truly harness its potential, it will be important to demonstrate that a single adult stem cell can, indeed, generate a line of genetically identical cells, which then gives rise to all the appropriate, differentiated cell types of the tissue in which it resides. Candidate adult stem cells can also be isolated and labeled and then transplanted back into the organism to determine what becomes of them. The current wave of excitement over the existence of stem cells in many adult tissues is perhaps fueling claims that progenitor or precursor cells in those tissues are instead stem cells. That realization has been triggered by a flurry of papers reporting that stem cells derived from one adult tissue can change their appearance and assume characteristics that resemble those of differentiated cells from other tissues.
Simply proving the existence of an adult stem cell population in a differentiated tissue is a laborious process.
Ultimately—and most importantly—it is necessary to demonstrate that the cells can integrate into their new tissue environment, survive in the tissue, and function like the mature cells of the tissue. The bone marrow stem cells may then differentiate into another mesodermally derived tissue such as skeletal muscle [28, 43], cardiac muscle [51, 71] or liver [4, 54, 97]. In both cases cited above, the cells would be deemed to show plasticity, but in the case of bone marrow stem cells generating brain cells, the finding is less predictable. Many of the experiments with CNS stem cells involve the formation of neurospheres, round aggregates of cells that are sometimes clonally derived. However, there is limited evidence to date that such adult stem cells can generate mature, fully functional cells or that the cells have restored lost function in vivo [54]. If the phenomenon of plasticity is to be used as a basis for generating tissue for transplantation, the techniques for doing it will need to be reproducible and reliable (see Chapter 10. Within the past five years, a series of studies has shown that stem cells occur in the adult mammalian brain and that these cells can generate its three major cell lineages [35, 48, 63, 66, 90, 96, 104] (see Chapter 8. Astrocytes are a kind of glial cell, which lend both mechanical and metabolic support for neurons; they make up 70 to 80 percent of the cells of the adult brain. Adjacent to the ependymal cell layer, in a region sometimes designated as the subependymal or subventricular zone, is a mixed cell population that consists of neuroblasts (immature neurons) that migrate to the olfactory bulb, precursor cells, and astrocytes. Traditionally, these astrocytes have been regarded as differentiated cells, not as stem cells and so their designation as stem cells is not universally accepted.
As long as a mitogen is present in the culture medium, the cells continue forming neurospheres without differentiating.
They have been described as non-dividing cells [24] that function as part of the blood-brain barrier [22].


Single, Dil+ ependymal cells isolated from the ventricular zone could also generate self-renewing neurospheres and differentiate into neurons and glia. A different pattern of scattered BrdU-labeled cells was observed in the spinal cord, which suggested that ependymal cells along the central canal of the cord occasionally divide and give rise to nearby ependymal cells, but do not migrate away from the canal. After injury, the ependymal cells in the spinal cord only give rise to astrocytes, not to neurons.
The new research utilizes a technique called representational difference analysis, together with cDNA microarray analysis, to monitor the patterns of gene expression in the complex tissue of the developing and postnatal mouse brain. In mice, when BrdU is used to label dividing cells in this region, about 50% of the labeled cells differentiate into cells that appear to be dentate gyrus granule neurons, and 15% become glial cells. The study involved autopsy material, obtained with family consent, from five cancer patients who had been injected with BrdU dissolved in saline prior to their death for diagnostic purposes.
This is certainly true in the brain [48], although it has not been demonstrated experimentally in many tissues. The normal development of the brain depends not only on the proliferation and differentiation of these fetal stem cells, but also on a genetically programmed process of selective cell death called apoptosis [76]. In a few experiments described as "preliminary," the human CNS stem cells were injected into the brains of immunosuppressed rats where they apparently differentiated into neuron-like cells or glial cells. The cells resumed proliferation and formed new neurospheres, thus establishing an in vitro system that (like the system established for mouse CNS neurospheres) could be maintained up to 2 years.
The cells differentiate into a range of tissues, not all of which are part of the nervous system [56, 57, 91]. They can self-renew (at least in the fetus) and can differentiate into multiple cells types, which include cells derived from two of the three embryonic germ layers [76].
Bone marrow stromal cells—a mixed cell population that generates bone, cartilage, fat, fibrous connective tissue, and the reticular network that supports blood cell formation—were described shortly after the discovery of HSCs [30, 32, 73]. The life of an animal literally depends on the ability of these and other blood cells to be replenished continuously. HSCs are defined by their ability to self-renew and to give rise to all the kinds of blood cells in the body. And for transplant purposes, cells that are CD34+ Thy1+ Lin- are most likely to contain stem cells and result in engraftment.
Myeloid precursors differentiate into monocytes and macrophages, neutrophils, eosinophils, basophils, megakaryocytes, and erythrocytes [3]. Many of the soluble factors that regulate HSC differentiation in vivo are cytokines, which are made by different cell types and are then concentrated in the bone marrow by the extracellular matrix of stromal cells—the sites of blood formation [45, 107]. Given specific in vitro conditions, BM stromal cells form colonies from a single cell called the colony forming unit-F (CFU-F).
Despite the use of these markers and another stromal cell marker called Stro-1, the origin and specific identity of stromal cells have remained elusive. When the skeleton stops growing, and the mass of HSCs decreases in a normal, age-dependent fashion, BM stromal cells differentiate into adipocytes, which fill the extra space. The embryonic vasculature formed at this stage is transient and consists of blood islands in the yolk sac.
A similar study using transgenic mice that express the gene for enhanced green fluorescent protein (which allows the cells to be tracked), showed that bone-marrow-derived cells could repopulate an area of infarcted heart muscle in mice, and generate not only blood vessels, but also cardiomyocytes that integrated into the host tissue [71] (see Chapter 9. When transplanted into mice of the same species (autologous transplants) with induced ischemia in one limb, the MBCD34+ cells promoted the formation of new blood vessels [8].
Although satellite cells are normally non-dividing, they can be triggered to proliferate as a result of injury, or weight-bearing exercise. For example, a recent report indicates that muscle stem cells may also occur in the dorsal aorta of mouse embryos, and constitute a cell type that gives rise both to muscle satellite cells and endothelial cells. Dystrophin is the protein that is defective in people with Duchenne's muscular dystrophy; mdx mice provide a model for the human disease.
Other epithelial cell populations—in the ducts of the liver or pancreas, for example—turn over more slowly. Their progeny can migrate down to the base of the follicle where they become matrix cells, which may then give rise to different cell types in the hair follicle, of which there are seven [39]. A dividing skin stem cell can divide asymmetrically to produce two kinds of daughter cells.
A recent study indicates that a single precursor cell derived from embryonic endoderm may generate both the ventral pancreas and the liver [23]. It is not known whether this kind of plasticity occurs without severe damage to the liver or whether HSCs from the bone marrow generate oval cells of the liver [18].
A candidate, universal adult stem cell may be one that circulates in the blood stream, can escape from the blood, and populate various adult tissues.
Activation, proliferation, and differentiation of progenitor cells into hepatocytes in the D-galactosamine model of liver regeneration.
Focus on a particular set of branches by applying a filter or temporarily collapsing other branches and add comments, pictures and formatted text notes at any time to illustrate or expand on specific points. In addition to the Multimedia Catalog, MindView contains a palette of icons, which you can place on the branches of your Mind Map to draw attention or illustrate a particular idea. Use the Pack & Go feature to save your Mind Map with all its attachments and share it with other users. Zoom in or out, expand or contract the timeline scale, or condense empty stretches of the timeline by inserting break marks. Efforts are now underway to harness stem cells and to take advantage of this new found capability, with the goal of devising new and more effective treatments for a host of diseases and disabilities. Shown here is an example of a hematopoietic stem cell producing a second generation stem cell and a neuron.
For example, HSCs are constantly being generated in the bone marrow where they differentiate into mature types of blood cells. Finally, candidate adult stem cells can be isolated, grown in vitro and manipulated, by adding growth factors or introducing genes that help determine what differentiated cells types they will yield.
Thus, there are reports of endothelial progenitor cells, skeletal muscle stem cells, epithelial precursors in the skin and digestive system, as well as some reports of progenitors or stem cells in the pancreas and liver.
It requires that the candidate stem cells are shown to be self-renewing, and that they can give rise to the differentiated cell types that are characteristic of that tissue.
Another way to separate population of bone marrow cells is by fractionation to yield cells that adhere to a growth substrate (stromal cells) or do not adhere (hematopoietic cells) [28]. But it is not possible to observe cells in the center of a neurosphere, so to study plasticity in vitro, the cells are usually dissociated and plated in monolayers. Most of the studies that show the plasticity of adult stem cells involve cells that are derived from the bone marrow [15, 28, 54, 65, 77] or brain [13, 17]. Oligodendrocytes make myelin, the fatty material that ensheathes nerve cell axons and speeds nerve transmission. During fetal development, the tissue adjacent to the ventricles is a prominent region of actively dividing cells.
The suggestion that ependymal cells from the ventricular zone of the adult rodent CNS may be stem cells is therefore unexpected. How and whether ependymal cells from the ventricular zone are related to other candidate populations of CNS stem cells, such as those identified in the hippocampus [34], is not known. The study revealed the expression of a panel of genes known to be important in CNS development, such as L3-PSP (which encodes a phosphoserine phosphatase important in cell signaling), cyclin D2 (a cell cycle gene), and ERCC-1 (which is important in DNA excision repair). Depending on the culture conditions, the cells in the neurospheres could be maintained in an undifferentiated dividing state (in the presence of mitogen), or dissociated and induced to differentiate (after the removal of mitogen and the addition of specific growth factors to the culture medium).
Neural crest cells form the sympathetic and parasympathetic components of the peripheral nervous system (PNS), including the network of nerves that innervate the heart and the gut, all the sensory ganglia (groups of neurons that occur in pairs along the dorsal surface of the spinal cord), and Schwann cells, which (like oligodendrocytes in the CNS) make myelin in the PNS.
At the earlier stage of development, the neural tube has formed, but neural crest cells have not yet migrated to their final destinations. The mesenchymal stem cells of the bone marrow also give rise to these tissues, and may constitute the same population of cells as the bone marrow stromal cells [78]. This replenishment process occurs largely in the bone marrow, where HSCs reside, divide, and differentiate into all the blood cell types.
This means that a single HSC is capable of regenerating the entire hematopoietic system, although this has been demonstrated only a few times in mice [72]. In vivo, bone marrow HSCs differentiate into mature, specialized blood cells that cycle constantly from the bone marrow to the blood, and back to the bone marrow [26].
Two of the most-studied cytokines are granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-3 (IL-3) [40, 81].
In addition to providing the physical environment in which HSCs differentiate, BM stromal cells generate cartilage, bone, and fat. These colonies may then differentiate as adipocytes or myelosupportive stroma, a clonal assay that indicates the stem cell-like nature of stromal cells. Like HSCs, BM stromal cells arise from embryonic mesoderm during development, although no specific precursor or stem cell for stromal cells has been isolated and identified. New bone formation is obviously greater during skeletal growth, although bone "turns over" throughout life. But hemangioblasts, per se, have not been isolated from the embryo and their existence remains in question. Although the adult MBCD34+ and MBFlk1+ cells function in some ways like stem cells, they are usually regarded as progenitor cells. Under either of these circumstances, muscle satellite cells give rise to myogenic precursor cells, which then differentiate into the myofibrils that typify skeletal muscle. Whether the dorsal aorta cells meet the criteria of a self-renewing muscle stem cell is a matter of debate [21]. Dystrophin expression in the SP cell-treated mice was lower than would be needed for clinical benefit. The cell population that renews the epithelium of the small intestine occurs in the intestinal crypts, deep invaginations in the lining of the gut.
In adult mammals, however, both the pancreas and the liver contain multiple kinds of differentiated cells that may be repopulated or regenerated by multiple types of stem cells. Although hepatic oval cells exist in the liver, it is not clear whether they actually generate new hepatocytes [87, 98].
In more than one experimental system, researchers have noted that dividing cells in adult tissues often appear near a blood vessel, such as candidate stem cells in the hippocampus, a region of the brain [75].
Cell proliferation and migration in the anterior forebrain, with special reference to persisting neurogenesis in the olfactory bulb. However, others can stand up for an hour and speak off the cuff about their subject, and make it interesting and memorable. Finally, MindView lets you highlight conceptual relationships between two or more branches by creating visual connections between them. You can use these ready-made plans for training purposes or as a basis for your own project plans. You can then export your timeline as an interactive HTML site, include it in a visual presentation, or print it out as a poster!
What lies ahead for the use of adult stem cells is unknown, but it is certain that there are many research questions to be answered and that these answers hold great promise for the future. Progenitor or precursor cells in fetal or adult tissues are partly differentiated cells that divide and give rise to differentiated cells. A progenitor cell (also known as a precursor cell) is unspecialized or has partial characteristics of a specialized cell that is capable of undergoing cell division and yielding two specialized cells. The list of adult tissues reported to contain stem cells is growing and includes bone marrow, peripheral blood, brain, spinal cord, dental pulp, blood vessels, skeletal muscle, epithelia of the skin and digestive system, cornea, retina, liver, and pancreas. For example, currently, scientists believe that stem cells in the fetal and adult brain divide and give rise to more stem cells or to several types of precursor cells, which give rise to nerve cells (neurons), of which there are many types. A detailed summary of some of the evidence for the existence of stem cells in various tissues and organs is presented later in the chapter. To study plasticity in vivo, the cells may be dissociated before injection into the circulatory system of the recipient animal [13], or injected as neurospheres [17]. To date, adult stem cells are best characterized in these two tissues, which may account for the greater number of plasticity studies based on bone marrow and brain. In some cases, debate continues about observations that adult stem cells yield cells of tissue types different than those from which they were obtained [7, 68].
Under normal, in vivo conditions, neuronal precursors do not give rise to glial cells, and glial precursors do not give rise to neurons. By adulthood, however, this tissue is much smaller, although it still appears to contain stem cells [70].
The astrocyte-like cells can be identified because they contain glial fibrillary acidic protein (GFAP), whereas the ependymal cells stain positive for nestin, which is regarded as a marker of neural stem cells. To induce differentiation into neurons or glia, cells are dissociated from the neurospheres and grown on an adherent surface in serum-free medium that contains specific growth factors. However, in a recent study, in which two molecular tags—the fluorescent marker Dil, and an adenovirus vector carrying lacZ tags—were used to label the ependymal cells that line the entire CNS ventricular system of adult rats, it was shown that these cells could, indeed, act as stem cells. All of these genes in the recent study were expressed in cultured neurospheres, as well as the ventricular zone, the subventricular zone, and a brain area outside those germinal zones.
Interestingly, many, if not all the BrdU-labeled cells in the adult rodent hippocampus occur next to blood vessels [33]. The greatest number of BrdU-labeled cells were identified in the oldest patient, suggesting that new neuron formation in the hippocampus can continue late in life [27]. The differentiated cells consisted mostly of astrocytes (75%), some neurons (13%) and rare oligodendrocytes (1.2%). Neural crest cells from early developmental stages are more sensitive to bone morphogenetic protein 2 (BMP2) signaling, which may help explain their greater differentiation potential [106].
Recently, a population of progenitor cells that differentiates into endothelial cells, a type of cell that lines the blood vessels, was isolated from circulating blood [8] and identified as originating in bone marrow [89].
Both HSCs and differentiated blood cells cycle from the bone marrow to the blood and back again, under the influence of a barrage of secreted factors that regulate cell proliferation, differentiation, and migration (see Chapter 5.
Telomerase is an enzyme that helps maintain the length of the ends of chromosomes, called telomeres, by adding on nucleotides. A recent study showed that short-term HSCs are a heterogeneous population that differ significantly in terms of their ability to self-renew and repopulate the hematopoietic system [42]. Whether stromal cells are best classified as stem cells or progenitor cells for these tissues is still in question. Unlike HSCs, which do not divide in vitro (or proliferate only to a limited extent), BM stromal cells can proliferate for up to 35 population doublings in vitro [16]. One theory about their origin is that a common kind of progenitor cell—perhaps a primordial endothelial cell that lines embryonic blood vessels—gives rise to both HSCs and to mesodermal precursors. Bone forming cells are osteoblasts, but their relationship to BM stromal cells is not clear. A group of transcription factors called myogenic regulatory factors (MRFs) play important roles in these differentiation events. Injection of bone marrow- or muscle-derived SP cells into the dystrophic muscle of the mice yielded equivocal results that the transplanted cells had integrated into the host tissue. The crypt cells are often regarded as stem cells; one of them can give rise to an organized cluster of cells called a structural-proliferative unit [93]. The second kind of daughter cell is an intermediate precursor cell which is then committed to replicate a few times before differentiating into keratinocytes. Oval cells may arise from the portal tracts in liver and may give rise to either hepatocytes [19, 55] and to the epithelium of the bile ducts [37, 92]. Such cells are usually regarded as "committed" to differentiating along a particular cellular development pathway, although this characteristic may not be as definitive as once thought [82] (see Figure 4.1. Collectively, studies on plasticity suggest that stem cell populations in adult mammals are not fixed entities, and that after exposure to a new environment, they may be able to populate other tissues and possibly differentiate into other cell types. In contrast, a fetal or adult CNS (central nervous system—the brain and spinal cord) stem cell may give rise to neurons, astrocytes, or oligodendrocytes, depending on the signals it receives and its three-dimensional environment within the brain tissue. Collectively, the studies demonstrate that a population of cells derived from the adult rodent brain can self-renew and differentiate to yield the three major cell types of the CNS cells [41, 69, 74, 102]. A few days after labeling, fluorescent or lacZ+ cells were observed in the rostral migratory stream (which leads from the lateral ventricle to the olfactory bulb), and then in the olfactory bulb itself. This analysis also revealed the expression of novel genes such as A16F10, which is similar to a gene in an embryonic cancer cell line.
The neurons generated under these conditions expressed markers indicating they were GABAergic, [the major type of inhibitory neuron in the mammalian CNS responsive to the amino acid neurotransmitter, gammaaminobutyric acid (GABA)]. They populate certain hormone-secreting glands—including the adrenal medulla and Type I cells in the carotid body—pigment cells of the skin (melanocytes), cartilage and bone in the face and skull, and connective tissue in many parts of the body [76].
Whether these endothelial progenitor cells, which resemble the angioblasts that give rise to blood vessels during embryonic development, represent a bona fide population of adult bone marrow stem cells remains uncertain. Active telomerase is a characteristic of undifferentiated, dividing cells and cancer cells.
There is also a question as to whether BM stromal cells and so-called mesenchymal stem cells are the same population [78]. They grow rapidly under the influence of such mitogens as platelet-derived growth factor (PDGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF), and insulin-like growth factor-1 (IGF-1) [12].
The latter may then differentiate into myogenic precursors (the satellite cells that are thought to function as stem cells in skeletal muscle), and the BM stromal cells [10]. New trabecular bone, which is the inner region of bone next to the marrow, could logically develop from the action of BM stromal cells. In the adult, the process of forming blood vessels from pre-existing blood vessels is called angiogenesis [50]. The so-called primary MRFs, MyoD and Myf5, help regulate myoblast formation during embryogenesis.
The authors conclude that a similar population of SP stem cells can be derived from either adult mouse bone marrow or skeletal muscle, and suggest "there may be some direct relationship between bone marrow-derived stem cells and other tissue- or organ-specific cells" [43]. Self-renewing stem cells can be distinguished from this intermediate precusor cell by their higher level of ?1 integrin expression, which signals keratinocytes to proliferate via a mitogen-activated protein (MAP) kinase [112]. They include the beta cells (which produce insulin), the alpha cells (which secrete glucagon), and cells that release the peptide hormones somatostatin and pancreatic polypeptide.
Indeed, hepatocytes themselves, may be responsible for the well-know regenerative capacity of liver.
OK, there are a few people who are natural public speakers, but for most of us, it takes a lot of preparation to stand up and speak clearly and concisely about our subject.
In contrast, stem cells in the small intestine are stationary, and are physically separated from the mature cell types they generate. The labeled cells in the olfactory bulb also stained for the neuronal markers ?III tubulin and Map2, which indicated that ependymal cells from the ventricular zone of the adult rat brain had migrated along the rostral migratory stream to generate olfactory bulb neurons in vivo [47]. A16F10 was expressed in neurospheres and at high levels in the subventricular zone, but not significantly in the ventricular zone.
However, catecholamine-like cells that express tyrosine hydroxylase (TH, a critical enzyme in the dopamine-synthesis pathway) could be generated, if the culture conditions were altered to include different medium conditioned by a rat glioma line (BB49). Thus, the bone marrow appears to contain three stem cell populations—hematopoietic stem cells, stromal cells, and (possibly) endothelial progenitor cells (see Figure 4.3. But the outside surface of bone also turns over, as does bone next to the Haversian system (small canals that form concentric rings within bone).
The secondary MRFs, myogenin and MRF4, regulate the terminal differentiation of myofibrils [86]. Thus, stem cell or progenitor cell types from various mesodermally-derived tissues may be able to generate skeletal muscle. Other signaling pathways include that triggered by -catenin, which helps maintain the stem-cell state [111], and the pathway regulated by the oncoprotein c-Myc, which triggers stem cells to give rise to transit amplifying cells [36]. Stem cells in the adult pancreas are postulated to occur in the pancreatic ducts or in the islets themselves. Gut epithelial stem cells (or precursors) occur at the bases of crypts—deep invaginations between the mature, differentiated epithelial cells that line the lumen of the intestine. However, there is no consensus about how many populations of CNS stem cells exist, how they may be related, and how they function in vivo. Interestingly, several of the genes identified in cultured neurospheres were also expressed in hematopoietic cells, suggesting that neural stem cells and blood-forming cells may share aspects of their genetic programs or signaling systems [38]. Thus, the report indicates that human CNS stem cells obtained from early fetuses can be maintained in vitro for a long time without differentiating, induced to differentiate into the three major lineages of the CNS (and possibly two kinds of neurons, GABAergic and TH-positive), and engraft (in rats) in vivo [103]. In adult humans, HSCs occur in the bone marrow, blood, liver, and spleen, but are extremely rare in any of these tissues. Several recent reports indicate that stem cells that express nestin—which is usually regarded as a marker of neural stem cells—can generate all of the cell types in the islets [60, 113] (see Chapter 7.
These epithelial crypt cells divide fairly often, but remain part of the stationary group of cells they generate [93]. Because there are no markers currently available to identify the cells in vivo, the only method for testing whether a given population of CNS cells contains stem cells is to isolate the cells and manipulate them in vitro, a process that may change their intrinsic properties [67].
This finding may help explain recent reports that CNS stem cells derived from mouse brain can give rise to hematopoietic cells after injection into irradiated mice [13].



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