Epidermal stem cells

Janes, Sam M.; Lowell, Sally; Hutter, Caroline

doi:10.1002/path.1156

Cited by 139 publications

(116 citation statements)

References 91 publications

(109 reference statements)

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“…Stem cells are present in many tissues where they function to maintain appropriate homeostasis and differentiation as well as regulate tissue responses to injury and infection (Watt and Hogan, 2000;Janes et al, 2002). These cells are capable of self-renewal, have a relatively undifferentiated phenotype, exhibit high proliferative potential, and are multipotent (Griffiths et al, 2005).…”

mentioning

confidence: 99%

Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade

et al. 2008

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Cancers are a heterogeneous mix of cells, some of which exhibit cancer stem cell-like characteristics including ATP-dependent drug efflux and elevated tumorigenic potential. To determine whether aerodigestive squamous cell carcinomas (SCCs) contain a subpopulation of cancer stem cell-like cells, we performed Hoechst dye efflux assays using four independent cell lines. Results revealed the presence of a rare, drug effluxing stem cell-like side population (SP) of cells within all cell lines tested (SCC-SP cells). These cells resembled previously characterised epithelial stem cells, and SCC-SP cell abundance was positively correlated with overall cellular density and individual cell quiescence. Serial SCC-SP fractionation and passaging increased their relative abundance within the total cell population. Purified SCC-SP cells also exhibited increased clonogenic potential in secondary cultures and enhanced tumorigenicity in vivo. Despite this, SCC-SP cells remained chemotherapeutically sensitive upon ATP-dependent transporter inhibition. Overall, these findings suggest that the existence of ATP transporter-dependent cancer stem-like cells may be relatively common, particularly within established tumours. Future chemotherapeutic strategies should therefore consider coupling identification and targeting of this potential stem cell-like population with standard treatment methodologies.

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confidence: 99%

Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade

et al. 2008

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“…Hence, both advantageous and deleterious mutations can represent steps toward cancer (14). Most human cancers arise in epithelial tissues, which are organized into small compartments of cells (15)(16)(17)(18)(19)(20)(21). In this article, we study how the architecture of cells within a compartment determines the evolutionary process of cancer initiation (14).…”

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confidence: 99%

The linear process of somatic evolution

Nowak

Michor

Iwasa

2003

Proc. Natl. Acad. Sci. U.S.A.

215

189

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Cancer is the consequence of an unwanted evolutionary process. Cells receive mutations that alter their phenotype. Especially dangerous are those mutations that increase the net reproductive rate of cells, thereby leading to neoplasia and later to cancer. The standard models of evolutionary dynamics consider well mixed populations of individuals in symmetric positions. Here we introduce a spatially explicit, asymmetric stochastic process that captures the essential architecture of evolutionary dynamics operating within tissues of multicellular organisms. The ''linear process'' has the property of canceling out selective differences among cells yet retaining the protective function of apoptosis. This design can slow down the rate of somatic evolution dramatically and therefore delay the onset of cancer.M utations in oncogenes and tumor suppressor genes can increase the net reproductive rate of cells (1-5) and therefore provide a selective advantage for mutated cells. Mutations in genes that maintain the integrity of the genome can trigger genetic instability (6-10), which may come at a selective cost but increases the chance of acquiring further mutations that are advantageous for the cell (11-13). Hence, both advantageous and deleterious mutations can represent steps toward cancer (14). Most human cancers arise in epithelial tissues, which are organized into small compartments of cells (15)(16)(17)(18)(19)(20)(21). In this article, we study how the architecture of cells within a compartment determines the evolutionary process of cancer initiation (14).Consider a compartment of N cells within a tissue of a multicellular organism. Suppose a mutation in a particular gene alters the reproductive rate of a cell. Wild-type and mutant cells have reproductive rates r 1 and r 2 , respectively. The relative fitness of mutant compared with wild type is s ϭ r 2 ͞r 1 ; it can be greater than, equal to, or less than one. The probability that the gene is mutated during cell division is given by u. To calculate the rate at which mutated cells accumulate, we have to define a specific stochastic process. Fig. 1a illustrates the Moran process (22). Any single time step consists of two elementary events: (i) a random cell is chosen for division proportional to its reproductive rate, and (ii) a random cell is chosen for elimination. Hence, the total number of cells is always constant. Division of a wild-type cell gives rise to a mutant cell with probability u. We ignore back mutation.Mutant cells are produced at rate Nu. The probability of fixation (taking over the whole population) of a single mutant cell with relative fitness s is given by ϭ (1 Ϫ 1/s)͞(1 Ϫ 1/s N ). The probability that a compartment of N cells has been taken over by mutant cells at time t is given by P(t) ϭ 1 Ϫ exp(ϪNu t). Time is measured in units of cellular generations. If t Ͻ Ͻ 1͞(Nu ), then the approximation P(t) Ϸ Nu t holds. This means that we are interested in time scales for which most cells of an organism are not yet mutated with respect to a particular ...

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“…This can range from 0.01% (haematopoietic SC) to 10% (epidermal SC), although the latter figure may be an overestimation. 2,3 One of the major attributes of SC is their potential to give rise to different cell lineages. This potency is however not equal among all SC and there exists among SC a hierarchy of potential.…”

mentioning

confidence: 99%

“…In the intestinal mucosa for example, it is believed that the pericryptal fibroblasts/subepithelial myofibroblasts may serve as niche cells, 6 and in the epidermis, beta 1 integrinmediated adhesion to its ligand, type IV collagen, is shown to influence behaviour of epidermal SC. 3 SC progeny migrate out from the niche and follow a path of differentiation. New genes are expressed with acquisition of differentiation markers.…”

mentioning

confidence: 99%

Stem cell differentiation and the effects of deficiency

Dua

Joseph

Shanmuganathan

et al. 2003

Eye

190

141

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Stem cells have several unique attributes, the key features being their potency and plasticity. They have the ability to give rise to multiple cell lineages and to transdifferentiate into totally different cell type(s) when relocated to a novel stem cell niche. Most self-renewing tissues are served by stem cells. At the ocular surface, the corneo-scleral limbus is believed to provide the niche for corneal epithelial stem cells. A large body of circumstantial evidence, both clinical and basic, supports this view. However, specific identification of limbal stem cells has proved elusive. Cytokeratin markers, vimentin, epidermal growth factor receptors, p63, and others have been used to identify epithelial cell populations at the limbus, which could harbour putative stem cells. In contrast, none of the known haematopoietic stem cell markers namely, CD34 and CD133, stain any specific subset of corneal or limbal epithelial cells. Singly or collectively, none of these markers point to any unique cell(s) that could be regarded as stem cells, supporting the notion that the corneal epithelium is served by 'committed progenitors' rather than by stem cells. Disease or destruction of the corneoscleral limbus is associated with consequential events that eventually lead to visual impairment or blindness. Conjunctivalisation and vascularisation of the corneal surface and persistent or recurring epithelial defects are hallmarks of limbal deficiency.

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Epidermal stem cells

Cited by 139 publications

References 91 publications

Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade

Squamous cell cancers contain a side population of stem-like cells that are made chemosensitive by ABC transporter blockade

The linear process of somatic evolution

Stem cell differentiation and the effects of deficiency

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