Stem cell-intrinsic mechanisms regulating adult hair follicle homeostasis.

Adult hair follicle stem cells (HFSCs) undergo dynamic and periodic molecular changes in their cellular states throughout the hair homeostatic cycle. These states are tightly regulated by cell-intrinsic mechanisms and by extrinsic signals from the microenvironment. HFSCs are essential not only for fuelling hair growth, but also for skin wound healing. Increasing evidence suggests an important role of HFSCs in organizing multiple skin components around the hair follicle, thus functioning as an organizing centre during adult skin homeostasis. Here, we focus on recent findings on cell-intrinsic mechanisms of HFSC homeostasis, which include transcription factors, histone modifications, DNA regulatory elements, non-coding RNAs, cell metabolism, cell polarity and post-transcriptional mRNA processing. Several transcription factors are now known to participate in well-known signalling pathways that control hair follicle homeostasis, as well as in super-enhancer activities to modulate HFSC and progenitor lineage progression. Interestingly, HFSCs have been shown to secrete molecules that are important in guiding the organization of several skin components around the hair follicle, including nerves, arrector pili muscle and vasculature. Finally, we discuss recent technological advances in the field such as single-cell RNA sequencing and live imaging, which revealed HFSC and progenitor heterogeneity and brought new light to understanding crosstalking between HFSCs and the microenvironment. The field is well on its way to generate a comprehensive map of molecular interactions that should serve as a solid theoretical platform for application in hair and skin disease and ageing.