Stem/Progenitor Cell-Like Properties of Desmoglein 3dim Cells in Primary and Immortalized Keratinocyte Lines

Wan, Hong; Yuan, Man; Simpson, Cathy A.; Allen, Kirsty; Gavins, Felicity N. E.; Ikram, Mohammed S.; Basu, Soumalee; Baksh, Nuzhat; O’Toole, Edel A.; Hart, Ian R.

doi:10.1634/stemcells.2006-0304

Cited by 30 publications

(34 citation statements)

References 55 publications

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“…These are a high-level expression of the Notch ligand Delta1, MCSP, and LRIG1, as well as a low expression of DSG3 (Lowell and Watt 2001;Legg et al 2003;Wan et al 2003Wan et al , 2007Jensen and Watt 2006;Estrach et al 2007). Analysis of expression of these markers in human IFE reveals that cells expressing high levels of clonogenic markers lie in irregular clusters localized around the tips of DP (Jones et al 1995;Legg et al 2003;Jensen and Watt 2006;Wan et al 2007). Strikingly, the great majority of cells within the clusters are quiescent, whereas proliferating cells lie between the clusters (Jensen et al 1999;Legg et al 2003).…”

Section: From Mouse To Human?mentioning

confidence: 99%

Lineage Analysis of Epidermal Stem Cells

Alcolea

Jones

2014

Cold Spring Harbor Perspectives in Medicine

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Lineage tracing involves labeling cells to track their subsequent behavior within the normal tissue environment. The advent of genetic lineage tracing and cell proliferation assays, together with high resolution three-dimensional (3D) imaging and quantitative methods to infer cell behavior from lineage-tracing data, has transformed our understanding of murine epidermal stem and progenitor cells. Here, we review recent insights that reveal how a progenitor cell population maintains interfollicular epidermis, whereas stem cells, quiescent under homeostatic conditions, are mobilized in response to wounding. We discuss progress in understanding how the various stem cell populations of the hair follicle sustain this complex and highly dynamic structure, and recent analysis of stem cells in sweat and sebaceous glands. The extent to which insights from mouse studies can be applied to human epidermis is also considered.

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Section: From Mouse To Human?mentioning

confidence: 99%

Lineage Analysis of Epidermal Stem Cells

Alcolea

Jones

2014

Cold Spring Harbor Perspectives in Medicine

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“…For example, HaCaT cells share molecular markers and phenotypes with stem/progenitor keratinocytes (20,21) and they also secret stem cell factor (22). In addition, TGF␤ induces differentiation of HaCaT cells, and use of HaCaT cells and their TGF␤-treated counterparts has yielded great insights into epithelial homeostasis (23)(24)(25).…”

Section: Tgf␤ Reverses the Function Of Klf5 From Pro-proliferative Tomentioning

confidence: 99%

Pro-proliferative Factor KLF5 Becomes Anti-proliferative in Epithelial Homeostasis upon Signaling-mediated Modification

Guo

Dong

Zhang

et al. 2009

Journal of Biological Chemistry

170

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During epithelial homeostasis, stem cells divide to produce progenitor cells, which not only proliferate to generate the cell mass but also respond to cellular signaling to transition from a proliferative state to a differentiation state. Such a transition involves functional alterations of transcriptional factors, yet the underlying molecular mechanisms are poorly understood. Recent studies have implicated Kruppel-like factors (KLFs) including KLF5 in the renewal and maintenance of stem/progenitor cells. Here we demonstrate that the pro-proliferative factor KLF5 becomes anti-proliferative upon TGF␤-mediated acetylation in an in vitro model of epithelial homeostasis. In the HaCaT epidermal cell line treated with or without TGF␤, we found that KLF5 was not only essential for cell proliferation, it was also indispensable for TGF␤-induced anti-proliferation in these cells. KLF5 inhibited the expression of p15 (CDKN2B), a cell cycle inhibitor, without TGF␤, but became a coactivator in TGF␤-induced p15 expression in the same cells. Mechanistically, TGF␤ recruited acetylase p300 to acetylate KLF5, and acetylation in turn altered the binding of KLF5 to p15 promoter, resulting in the reversal of KLF5 function. These studies not only demonstrate that a basic transcription factor can be both pro-proliferation and anti-proliferation in epithelial homeostasis, they also present a unique mechanism for how transcriptional regulation changes during the transition from proliferation to inhibition of proliferation. Furthermore, they establish KLF5 as an essential cofactor for TGF␤ signaling.Epithelia constitute the surface and lining of many solid tissues and have essential functions in different tissues. They are maintained through epithelial homeostasis, which involves the proliferation of stem/progenitor cells and the differentiation of their daughter cells. Epithelial homeostasis constantly occurs in vivo, and its disruption causes different diseases including cancer (1). At the molecular level, signaling from stroma compartment in a tissue such as transforming growth factor ␤ (TGF␤) 2 signaling regulates epithelial homeostasis through a transcriptional network, but the molecular details are not well understood.The basic transcription factor KLF5 is ubiquitously expressed in many tissues including the breast, colon, intestine, lung, prostate, etc (2-5). KLF5 is highly expressed in proliferating epithelial cells such as immortal but untransformed epithelial cell lines and proliferating primary cultures of epithelial cells, which mostly represent progenitor cells (2, 3, 6, 7). In normal intestine, KLF5 is expressed at a higher level in basal rapidly proliferating cells, but at a lower level in mature and differentiated cells (8) and knock-out of one KLF5 allele significantly reduced the size of villi in mouse intestine (8). In vivo overexpression of KLF5 in epidermis causes hyperplasia of basal cells but lack of mature skin (9), further indicating a proproliferative role of KLF5 in epithelial homeostasis. Recently a combinatio...

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“…High β1-integrin expressing human keratinocytes have been shown to express low levels of Dsg3 and exhibit greater long-term proliferative capacity in vitro than integrin β1 hi /Dsg3 hi cells. The β1 hi /Dsg3 lo cells isolated from the adult human palm show comparable clonogenic ability to α6 hi /CD71 lo cells [121,122]. Some evidence suggests that CD146, melanoma cell adhesion molecule (MCAM), may also distinguish stem cells.…”

Section: Introduction — the Epidermismentioning

confidence: 99%

Biochemistry of epidermal stem cells

Eckert

Adhikary

Balasubramanian

et al. 2013

Biochimica et Biophysica Acta (BBA) - General Subjects

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Background The epidermis is an important protective barrier that is essential for maintenance of life. Maintaining this barrier requires continuous cell proliferation and differentiation. Moreover, these processes must be balanced to produce a normal epidermis. The stem cells of the epidermis reside in specific locations in the basal epidermis, hair follicle and sebaceous glands and these cells are responsible for replenishment of this tissue. Scope of review A great deal of effort has gone into identifying protein epitopes that mark stem cells, in identifying stem cell niche locations, and in understanding how stem cell populations are related. We discuss these studies as they apply to understanding normal epidermal homeostasis and skin cancer. Major conclusions An assortment of stem cell markers have been identified that permit assignment of stem cells to specific regions of the epidermis, and progress has been made in understanding the role of these cells in normal epidermal homeostasis and in conditions of tissue stress. A key finding is the multiple stem cell populations exist in epidermis that give rise to different structures, and that multiple stem cell types may contribute to repair in damaged epidermis. General significance Understanding epidermal stem cell biology is likely to lead to important therapies for treating skin diseases and cancer, and will also contribute to our understanding of stem cells in other systems. This article is part of a Special Issue entitled Biochemistry of Stem Cells.

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Stem/Progenitor Cell-Like Properties of Desmoglein 3dim Cells in Primary and Immortalized Keratinocyte Lines

Cited by 30 publications

References 55 publications

Lineage Analysis of Epidermal Stem Cells

Lineage Analysis of Epidermal Stem Cells

Pro-proliferative Factor KLF5 Becomes Anti-proliferative in Epithelial Homeostasis upon Signaling-mediated Modification

Biochemistry of epidermal stem cells

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