Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling

Festa, Eric; Fretz, Jackie A.; Berry, Ryan; Schmidt, B.; Rodeheffer, Matthew S.; Horowitz, Mark C.; Horsley, Valerie

doi:10.1016/j.cell.2011.07.019

Cited by 538 publications

(676 citation statements)

References 42 publications

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“…Adipose tissues promote wound healing by mediating fibroblast migration and further contribute to hair follicle regeneration. [44,45] Overall, our approach to investigate immune-modulated hydrogel yielded the development of a pro-regenerative Dex-IEME hydrogel. This hydrogel has the capacity to lead to greater success in skin regeneration and the attenuation of scar formation during deep wound healing.…”

Section: Discussionmentioning

confidence: 99%

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Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous Wound Healing

Sun

2017

Adv Healthcare Materials

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The transformation of fibrotic healing process to regenerative one has great potential to fully restore wounded skin. The M2 macrophage phenotype promotes constructive tissue remodeling and instructs tissue repair in a regenerative manner. It is hypothesized that hydrogels that can establish robustness of endogenous cells to regulate M2 phenotype will promote constructive dermal remodeling. Toward this end, a series of dextran‐based bioabsorbable hydrogels are developed and self‐crosslinkable dextran‐isocyanatoethyl methacrylate‐ethylamine (DexIEME) is identified as the potential scaffold. The initial screening study revealed that DexIEME has superior biocompatibility in varying concentrations. Although DexIEME brings about low proinflammatory responses, it promotes M2 macrophage phenotype. Then the optimized hydrogel formulation is tested for acute skin injuries using both murine and porcine models. Preliminary data demonstrated that the innovative DexIEME hydrogel promotes complete skin regeneration with hair regrowth on pre‐existing scars, while untreated scars remain intact. Preclinical studies further demonstrated that the DexIEME hydrogel regenerated perfect skin during deep porcine wound healing. Overall, the approach to investigate immune‐modulated hydrogels yields pro‐regenerative DexIEME hydrogel, which may lead to greater clinical success in treating deep dermal injury and attenuating scar formation.

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Section: Discussionmentioning

confidence: 99%

“…[44,45] To further examine the biocompatibility of dextran derivatives, the proliferation of human adipose stem cells (ASCs) (Cyagen Biosciences Technology) was detected using the MTS kit (Sigma). ASCs were cultured in DMEM/F-12 containing 10% fetal bovine serum until the cells reached 80% confluence.…”

Section: Methodsmentioning

confidence: 99%

Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous Wound Healing

Sun

2017

Adv Healthcare Materials

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“…Additionally, neither the downstream signaling pathways nor the cellular targets of Prl in the native hair cycle have been elucidated. Prl has been reported to signal through Akt (Acosta et al 2003;Chakravarti et al 2005;Chen et al 2012) and Map kinase (Das and Vonderhaar 1995), both of which are activated in bulge cells during the native hair cycle (Affara et al 2006;Festa et al 2011) and may act downstream from Prl. Adding further complexity to the matter are reports of local Prl expression in human skin (Foitzik et al 2006) that suggest that Prl can also signal in an autocrine or paracrine manner.…”

Section: Endocrine Control Of Skin Sc Functionmentioning

confidence: 99%

“…After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http:// creativecommons.org/licenses/by-nc/4.0/. and dermal adipocytes (Plikus et al 2008;Festa et al 2011). Interestingly, hormonal changes associated with pregnancy and lactation can alter skin tissue biology, notably through the stalling of HF growth in mice (Plikus et al 2008).…”

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confidence: 99%

Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation

et al. 2014

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In most tissues, the prevailing view is that stem cell (SC) niches are generated by signals from within the nearby tissue environment. Here, we define genetic changes altered in hair follicle (HF) SCs in mice treated with a potent SC activator, cyclosporine A (CSA), which inhibits the phosphatase calcineurin (CN) and the activity of the transcription factor nuclear factor of activated T cells c1 (Nfatc1). We show that CN/Nfatc1 regulates expression of prolactin receptor (Prlr) and that canonical activation of Prlr and its downstream signaling via Jak/Stat5 drives quiescence of HF SCs during pregnancy and lactation, when serum prolactin (Prl) levels are highly elevated. Using Prl injections and genetic/pharmacological loss-of-function experiments in mice, we show that Prl signaling stalls follicular SC activation through its activity in the skin epithelium. Our findings define a unique CN-Nfatc1-PrlrStat5 molecular circuitry that promotes persistent SC quiescence in the skin.

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“…Real-time PCR was performed as described (Festa et al, 2011). Briefly, total RNAs were isolated with Trizol (Invitrogen) and RNeasy kit (Qiagen) from FACS-sorted embryonic non-neural ectoderm, embryonic keratinocytes and from plated undifferentiated or differentiated hESCs.…”

Section: Quantitative Reverse Transcription-pcrmentioning

confidence: 99%

Notch signaling represses p63 expression in the developing surface ectoderm

Tadeu

Horsley

2013

Development

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MiceK14-H2BGFP transgenic mice (Tumbar et al., 2004) SUMMARYThe development of the mature epidermis requires a coordinated sequence of signaling events and transcriptional changes to specify surface ectodermal progenitor cells to the keratinocyte lineage. The initial events that specify epidermal keratinocytes from ectodermal progenitor cells are not well understood. Here, we use both developing mouse embryos and human embryonic stem cells (hESCs) to explore the mechanisms that direct keratinocyte fate from ectodermal progenitor cells. We show that both hESCs and murine embryos express p63 before keratin 14. Furthermore, we find that Notch signaling is activated before p63 expression in ectodermal progenitor cells. Inhibition of Notch signaling pharmacologically or genetically reveals a negative regulatory role for Notch signaling in p63 expression during ectodermal specification in hESCs or mouse embryos, respectively. Taken together, these data reveal a role for Notch signaling in the molecular control of ectodermal progenitor cell specification to the epidermal keratinocyte lineage.

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Adipocyte Lineage Cells Contribute to the Skin Stem Cell Niche to Drive Hair Cycling

Cited by 538 publications

References 42 publications

Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous Wound Healing

Pro‐Regenerative Hydrogel Restores Scarless Skin during Cutaneous Wound Healing

Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation

Notch signaling represses p63 expression in the developing surface ectoderm

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