The adult hair follicle (HF) undergoes successive regeneration driven by resident epithelial stem cells and neighboring mesenchyme. Recent work described the existence of HF dermal stem cells (hfDSCs), but the genetic regulation of hfDSCs and their daughter cell lineages in HF regeneration remains unknown. Here we prospectively isolate functionally distinct mesenchymal compartment in the HF (dermal cup [DC; includes hfDSCs] and dermal papilla) and define the transcriptional programs involved in hfDSC function and acquisition of divergent mesenchymal fates. From this, we demonstrate cross-compartment mesenchymal signaling within the HF niche, whereby DP-derived R-spondins act to stimulate proliferation of both hfDSCs and epithelial progenitors during HF regeneration. Our findings describe unique transcriptional programs that underlie the functional heterogeneity among specialized fibroblasts within the adult HF and identify a novel regulator of mesenchymal progenitor function during tissue regeneration.

成年毛囊 (HF) 经历由常驻上皮干细胞和邻近间充质驱动的连续再生。最近的工作描述了 HF 真皮干细胞 (hfDSCs) 的存在，但 hfDSCs 及其子细胞谱系在 HF 再生中的遗传调控仍然未知。在这里，我们前瞻性地分离了 HF（真皮杯 [DC；包括 hfDSCs] 和真皮乳头）中功能不同的间充质区室，并定义了参与 hfDSC 功能和获得不同间充质命运的转录程序。由此，我们证明了 HF 生态位内的跨室间充质信号传导，由此 DP 衍生的 R-spondins 在 HF 再生过程中刺激 hfDSC 和上皮祖细胞的增殖。