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Global analysis of genome accessibility in hair follicle stem cells

ABSTRACT: Quiescent stem cells are periodically activated to maintain tissue homeostasis or occasionally called into action upon injury. Molecular mechanisms that constitutively maintain stem cell identity or promote stem cell proliferation and differentiation upon activation have been extensively studied. However, it is unclear how quiescent stem cells maintain identity and reinforce quiescence when they transition from quiescence to activation. Here we show mouse hair follicle stem cell compartment induces a transcription factor, Foxc1, when activated. Importantly, deletion of Foxc1 in the activated but not quiescent stem cells compromises stem cell identity, fails to re-establish quiescence and subsequently drives premature stem cell activation.These findings uncover a dynamic, cell-intrinsic mechanism employed by hair follicle stem cells to reinforce stemness in response to activation.

ORGANISM(S): Mus musculus

PROVIDER: GSE68288 | GEO | 2016/02/05

SECONDARY ACCESSION(S): PRJNA282385

REPOSITORIES: GEO

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Foxc1 reinforces quiescence in hair follicle stem cells

Project description:Quiescent stem cells are periodically activated to maintain tissue homeostasis or occasionally called into action upon injury. Molecular mechanisms that constitutively maintain stem cell identity or promote stem cell proliferation and differentiation upon activation have been extensively studied. However, it is unclear how quiescent stem cells maintain identity and reinforce quiescence when they transition from quiescence to activation. Here we show mouse hair follicle stem cell compartment induces a transcription factor, Foxc1, when activated. Importantly, deletion of Foxc1 in the activated but not quiescent stem cells compromises stem cell identity, fails to re-establish quiescence and subsequently drives premature stem cell activation.These findings uncover a dynamic, cell-intrinsic mechanism employed by hair follicle stem cells to reinforce stemness in response to activation. Poly(A)-enriched transcriptome RNA-seq on HFSCs isolated in WT and K14Cre cKO mice at anagen and early telogen stage of hair cycle.

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2011-09-01 | E-GEOD-31028 | biostudies-arrayexpress

Stem cell quiescence acts as a tumor suppressor mechanism in hair follicle initiated squamous tumors

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Stem Cell Quiescence acts as a tumor suppressor mechanism in hair follicle initiated squamous tumors

Project description:In some organs, adult stem cells are uniquely poised to serve as cancer cells of origin1-4. It is unclear, however, whether tumorigenesis is influenced by the activation state of the adult stem cell. Hair follicle stem cells (HFSCs) act as cancer cells of origin for cutaneous squamous cell carcinoma (SCC) and undergo defined cycles of quiescence and activation. The data presented here show that HFSCs are unable to initiate tumors during the quiescent phase of the hair cycle, indicating that the mechanisms that keep HFSCs dormant are dominant to the gain of oncogenes (Ras) or the loss of tumor suppressors (p53). Furthermore, Pten activity is necessary for quiescence based tumor suppression, as its deletion alleviates tumor suppression without affecting proliferation. These data demonstrate that stem cell quiescence is a form of tumor suppression in HFSCs, and that Pten plays a role in maintaining quiescence in the presence of tumorigenic stimuli. This experiment includes RNA profiling of hair follicle stem cells at various stages of tumorigenesis

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