title: Calcineurin/Nfatc1 signaling links skin stem cell quiescence to hormonal signaling during pregnancy and lactation.
abstract: 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-Prlr-Stat5 molecular circuitry that promotes persistent SC quiescence in the skin.
authors.affiliation: Department of Molecular, Cell, and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Jill
authors.initials: J
authors.lastname: Goldstein
authors.forename: Sean
authors.initials: S
authors.lastname: Fletcher
authors.forename: Eve
authors.initials: E
authors.lastname: Roth
authors.forename: Christine
authors.initials: C
authors.lastname: Wu
authors.forename: Andrew
authors.initials: A
authors.lastname: Chun
authors.forename: Valerie
authors.initials: V
authors.lastname: Horsley
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000235:genetics / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D018859:Hair Follicle / Q000166:cytology* / Q000187:drug effects; D006728:Hormones / Q000494:pharmacology; D053612:Janus Kinases / Q000378:metabolism; D007774:Lactation / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D011388:Prolactin / Q000097:blood / Q000494:pharmacology; D011981:Receptors, Prolactin / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects
chemical_list: D006728:Hormones; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D011981:Receptors, Prolactin; D050799:STAT5 Transcription Factor; D016572:Cyclosporine; D011388:Prolactin; D053612:Janus Kinases; D019703:Calcineurin
keywords: Nfatc1; Stat5; calcineurin; cyclosporine; hair follicle; prolactin; stem cell
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