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What is a stem cell?

Overview

Jonathan M. W. Slack

Published Online: May 15 2018

DOI: 10.1002/wdev.323

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The historical roots of the stem cell concept are traced with respect to its usage in embryology and in hematology. The modern consensus definition of stem cells, comprising both pluripotent stem cells in culture and tissue‐specific stem cells in vivo, is explained and explored. Methods for identifying stem cells are discussed with respect to cell surface markers, telomerase, label retention and transplantability, and properties of the stem cell niche are explored. The CreER method for identifying stem cells in vivo is explained, as is evidence in favor of a stochastic rather than an obligate asymmetric form of cell division. In conclusion, it is found that stem cells do not possess any unique and specific molecular markers; and stem cell behavior depends on the environment of the cell as well as the stem cell's intrinsic qualities. Furthermore, the stochastic mode of division implies that stem cell behavior is a property of a cell population not of an individual cell. In this sense, stem cells do not exist in isolation but only as a part of multicellular system. This article is categorized under: Adult Stem Cells, Tissue Renewal, and Regeneration > Tissue Stem Cells and Niches Adult Stem Cells, Tissue Renewal, and Regeneration > Methods and Principles Adult Stem Cells, Tissue Renewal, and Regeneration > Environmental Control of Stem Cells

Different kinds of pluripotent stem cells. (a) Mouse ESC. (b) Mouse iPSC. (c) Human iPSC induced to a naive pluripotent state with chemical inhibitors. (d) Human ESC. (e) Human iPSC. (f) Mouse EpiSC. Note the flatter colony morphology for (d)–(f). (Reprinted with permission from Robinton and Daley (). Copyright 2012 Nature Publishing Group)

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A consensus diagram showing stem cell behavior. The stem cell exists in a specific niche which enables it to undergo self‐renewing divisions. It also generates differentiated cells via a population of committed but still dividing transit‐amplifying cells. Not all stem cell types generate multiple types of differentiated cell

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A portion of figure 135 from “The Cell in Development and Heredity” by Wilson (). This shows the term “stem cell” being used to describe early divisions of embryo blastomeres leading to the germ line

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Mentions of “stem cell” in the abstracts of all papers in the Web of Science Core collection. The totals are shown in five yearly intervals and rise from 372 in 1977–1982 to 71,545 in 2012–2016

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Stochastic stem cell model. (a) The four types of stem cell division, producing two, one or no daughter stem cells. (b) Disappearance of labeled clone, and doubling of size of labeled clone. (c) Consequent tendency of labeled clones to become fewer but larger with time

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Lineage tracing of epidermal stem cells in mouse skin. The mice express Axin2‐CreER with an R26R type reporter expressing GFP (green) following Cre mediated recombination. The blue color is DAPI stain for cell nuclei, and the red is immunostaining for Dickkopf3, a Wnt inhibitor present in the superficial layers. Tamoxifen was given on postnatal day 21 and the images show the situation at 1 day and 2 months thereafter. (a) 1 day, a few basal layer cells are labeled. (b) 2 months, clones of labeled cells are visible leading from the basal layer to the surface. (Reprinted with permission from Lim et al. (). Copyright 2013 American Association for the Advancement of Science)

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Descendants of stem cells in the mouse intestine visualized by the CreER method. The stem cells express a protein, LGR5 whose promoter is used for labeling. (a) The mice were labeled 1 day previously, in (b) 5 days previously, and in (c) 60 days previously. The initial label is in the LGR5 positive cells themselves (arrows); subsequently, ribbons of descendant cells up the crypts and villi become labeled. (Reprinted with permission from Barker et al. (). Copyright 2007 Nature Publishing Group)

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The stem cell niche in the Drosophila ovary. Female germ cell stem cells require continued contact with cap cells to remain stem cells. Once they lose contact with cap cells they differentiate into a cyst of 1 oocyte and 15 nurse cells

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Hematopoietic stem cell, identified by staining with an antibody to CD150 (red), and also labeled with EdU (white) from a pulse given 30 days previously. The green color shows pericytes expressing nestin‐GFP surrounding a small arteriole. (Reprinted with permission from Kunisaki et al. (). Copyright 2013 Nature Publishing Group)

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