Foxc1 reinforces quiescence in hair follicle stem cells

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.静息干细胞（quiescent stem cells）会周期性激活以维持组织稳态（tissue homeostasis），或在机体损伤时被临时征召发挥功能。针对组成性维持干细胞身份，或在激活状态下促进干细胞增殖与分化的分子机制，学界已开展了广泛研究。然而，目前尚不清楚静息干细胞在从静息状态向激活状态转变的过程中，如何维持自身身份并强化静息状态。本研究发现，小鼠毛囊干细胞区室（hair follicle stem cell compartment）在激活时会诱导转录因子Foxc1的表达。值得注意的是，在激活态而非静息态干细胞中敲除Foxc1，会损害干细胞身份、无法重新建立静息状态，并最终促使干细胞提前激活。上述研究结果揭示了毛囊干细胞响应激活时所采用的一种动态、细胞自主性的干性强化机制。本研究对处于毛发周期生长期（anagen）和早期休止期（early telogen）的野生型（WT）与K14-Cre条件性敲除（K14Cre cKO）小鼠来源的毛囊干细胞（HFSCs）开展了Poly(A)富集转录组RNA-seq分析。