Epithelial Stem Cells in Adult Skin

Tadeu, Ana; Horsley, Valerie

doi:10.1016/b978-0-12-416022-4.00004-4

Cited by 38 publications

(36 citation statements)

References 132 publications

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“…In addition, expression of the Wnt ligand, Wnt 7b, and the downstream Wnt effector/target gene, LEF1, were up-regulated following poly (I:C) treatment of keratinocytes (Fig. 5C–E) (Barker and Clevers, 2010; Tadeu and Horsley, 2014). Similarly, expression of Shh pathway components SHH and GLI1 was increased following poly (I:C) addition, as was the expression of EDAR, another gene active in skin appendage formation (Fig.…”

Section: Resultsmentioning

confidence: 97%

“…Following treatment with poly (I:C), keratinocytes expressed markers associated with hair progenitors including leucine-rich-repeat containing G proteins (LGR) 5 and 6 (Fig 4F) (Tadeu and Horsley, 2014). Induction of LGR6 is particularly notable, as previous lineage tracing experiments demonstrated that LGR6 expressing cells contribute to regenerating hair follicles during WIHN (Snippert et al, 2010).…”

Section: Resultsmentioning

confidence: 99%

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dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration

et al. 2015

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Regeneration of skin and hair follicles after wounding - a process known as wound-induced hair neogenesis (WIHN) - is a rare example of adult organogenesis in mammals. As such, WIHN provides a unique model system for deciphering mechanisms underlying mammalian regeneration. Here, we show that dsRNA, which is released from damaged skin, activates Toll-Like Receptor 3 (TLR3) and its downstream effectors IL6 and STAT3 to promote hair follicle regeneration. Conversely, TLR3-deficient animals fail to initiate WIHN. TLR3 activation promotes expression of hair follicle stem cell markers and induces elements of the core hair morphogenetic program, including EDAR and the Wnt and Shh pathways. Our results therefore show that dsRNA and TLR3 link the earliest events of mammalian skin wounding to regeneration and suggest potential therapeutic approaches for promoting hair neogenesis.

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Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration

et al. 2015

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“…In the IFE, these long-lived ESC give rise to progenitors with increased proliferative capacities that differentiate into keratinocytes as they migrate upward into suprabasal layers. Numerous studies have addressed the role of several key signaling pathways, such as those implicating bone morphogenetic proteins, TGF-β, Notch, Sonic Hedgehog, or Wnt in skin homeostasis, and how they control ESC maintenance (1)(2)(3). The role of these pathways in regulating stemness has been attributed to the regulation of cell proliferation, cell death, cellular senescence, cell adhesion, or differentiation.…”

mentioning

confidence: 99%

E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis

Goguet-Rubio

Seyran

Gayte

et al. 2016

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

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The multifunctional protein E4 transcription factor 1 (E4F1) is an essential regulator of epidermal stem cell (ESC) maintenance. Here, we found that E4F1 transcriptionally regulates a metabolic program involved in pyruvate metabolism that is required to maintain skin homeostasis. E4F1 deficiency in basal keratinocytes resulted in deregulated expression of dihydrolipoamide acetyltransferase (Dlat), a gene encoding the E2 subunit of the mitochondrial pyruvate dehydrogenase (PDH) complex. Accordingly, E4f1 knock-out (KO) keratinocytes exhibited impaired PDH activity and a redirection of the glycolytic flux toward lactate production. The metabolic reprogramming of E4f1 KO keratinocytes associated with remodeling of their microenvironment and alterations of the basement membrane, led to ESC mislocalization and exhaustion of the ESC pool. ShRNA-mediated depletion of Dlat in primary keratinocytes recapitulated defects observed upon E4f1 inactivation, including increased lactate secretion, enhanced activity of extracellular matrix remodeling enzymes, and impaired clonogenic potential. Altogether, our data reveal a central role for Dlat in the metabolic program regulated by E4F1 in basal keratinocytes and illustrate the importance of PDH activity in skin homeostasis.enewal and wound healing of the epidermis rely on a pool of epidermal stem cells (ESC) located in the basal layer of the interfollicular epithelium (IFE) and in the bulge region of the hair follicle (HF). In the IFE, these long-lived ESC give rise to progenitors with increased proliferative capacities that differentiate into keratinocytes as they migrate upward into suprabasal layers. Numerous studies have addressed the role of several key signaling pathways, such as those implicating bone morphogenetic proteins, TGF-β, Notch, Sonic Hedgehog, or Wnt in skin homeostasis, and how they control ESC maintenance (1-3). The role of these pathways in regulating stemness has been attributed to the regulation of cell proliferation, cell death, cellular senescence, cell adhesion, or differentiation. Although previous data indicate that some of these stem cell regulators also control energy metabolism in the hematopoietic or neuronal lineages (4), very few studies have yet addressed their metabolic functions in keratinocytes. In addition, the potential role of specific metabolic regulators in the control of skin homeostasis remains poorly documented. Nevertheless, previous observations indicate that deregulation of the nutrient-sensing mammalian target of rapamycin pathway in basal keratinocytes occurs as a consequence of prolonged Wnt signaling, leading to the progressive exhaustion of HF bulge stem cells (5). Recent data also indicate that genetic inactivation in mouse epidermis of mitochondrial transcription factor A (Tfam), a gene involved in mitochondrial DNA replication and transcription, impinges on keratinocyte differentiation but does not impair maintenance of basal keratinocytes (6). Although these results suggest that basal keratinocytes display a metabolic st...

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“…The outer epithelial layer of human skin is continuously developed and renewed by differentiating basal layer stem cells (Tadeu and Horsley, 2014). Accordingly, every day humans shed significant numbers of cells that contain DNA, epidermal proteins and mRNA.…”

Section: Introductionmentioning

confidence: 99%

Human skin identification using specific gene marker at different storage temperatures

Ibrahim

2018

Egypt J Forensic Sci

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Background: Late cornified envelope 1D (LCE1D), skin-specific mRNA, is used in forensic researche on human skin cell identification. Before using (LCE1D) in criminal casework, the impact of storage conditions on its expression should be measured and assessed. To detect the effects of storage temperature and duration, skin swabs were collected from six volunteers and stored at room temperature (25°C) and warmer temperature (40°C) for 5 days. Results: The (LCE1D) expressions, detected via Real Time PCR, were significantly diminished by increased storage duration. While there were also decreased (LCE1D) expressions among warmer temperature samples, this difference was not statistically significant. Conclusion: Our results suggest that forensic investigators should consider sample collection time prior to result interpretation.

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Epithelial Stem Cells in Adult Skin

Cited by 38 publications

References 132 publications

dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration

dsRNA Released by Tissue Damage Activates TLR3 to Drive Skin Regeneration

E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis

Human skin identification using specific gene marker at different storage temperatures

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