Hagner Andrew, Shin Wisoo, Sinha Sarthak, Alpaugh Whitney, Workentine Matthew, Abbasi Sepideh, Rahmani Waleed, Agabalyan Natacha, Sharma Nilesh, Sparks Holly, Yoon Jessica, Labit Elodie, Cobb John, Dobrinski Ina, Biernaskie Jeff
Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, AB, Canada.
Department of Biological Sciences, University of Calgary, Calgary, AB, Canada.
iScience. 2020 Apr 24;23(4):101019. doi: 10.1016/j.isci.2020.101019. Epub 2020 Apr 2.
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.
成体毛囊（HF）在驻留上皮干细胞和邻近间充质的驱动下经历连续再生。最近的研究描述了毛囊真皮干细胞（hfDSCs）的存在，但hfDSCs及其子代细胞谱系在毛囊再生中的基因调控仍不清楚。在这里，我们前瞻性地分离出毛囊中功能不同的间充质区室（真皮杯[DC；包括hfDSCs]和真皮乳头），并确定参与hfDSC功能和不同间充质命运获得的转录程序。据此，我们证明了毛囊生态位内的跨区室间充质信号传导，即真皮乳头衍生的R-spondins在毛囊再生过程中刺激hfDSCs和上皮祖细胞的增殖。我们的研究结果描述了独特的转录程序，这些程序是成体毛囊内特殊成纤维细胞功能异质性的基础，并确定了组织再生过程中间充质祖细胞功能的一种新调节因子。
