MicroRNA-205 promotes hair regeneration by modulating mechanical properties of hair follicle stem cells

Abstract

Stiffness and actomyosin contractility are intrinsic mechanical properties of animal cells required for the shaping of tissues. However, whether tissue stem cells (SCs) and progenitors located within SC niche have different mechanical properties that govern their size and functions remains unclear. We show that hair follicle SCs in the bulge are stiff with high actomyosin contractility and resistant to size change, whereas hair germ (HG) progenitors are soft and periodically enlarge and contract during quiescence. During activation, HGs reduce contraction and more frequently enlarge, a process that is associated with weakening of the actomyosin network, nuclear YAP accumulation and cell cycle re-entry. Induction of miR-205, a novel regulator of the actomyosin cytoskeleton, reduces actin contractility, decreases the stiffness of the bulge and HG, and activates hair regeneration in young and old mice. This study reveals the control of tissue SC size and activities by spatiotemporally compartmentalized mechanical properties and demonstrates the possibility to stimulate tissue regeneration by fine-tuning cell mechanics.

Single cell analysis of transcriptome and open chromatin reveals the dynamics of hair follicle stem cell aging

“…To capture the dynamic changes among the full spectrum of hair follicle cells during aging, we employed flow cytometry to sort epithelial cells, marked by H2B-GFP from Krt14-H2B-GFP mice, at postnatal day 38 (P38 male, synchronized catagen) (Zhang et al, 2021), P53 (female, synchronized telogen) (Wang et al, 2023), 6 months (female, mostly anagen HFs), 12 months (male, mixed telogen and anagen), and 24 months (female, mostly telogen). Single-cell RNA sequencing (scRNAseq) libraries were generated using the 10X Genomics Chromium platform (see Supplementary Table S1).…”

“…Genetic deletion of DNA methyltransferase 1 (DNMT1), on the other hand, decreases HF-SC activation and leads to progressive alopecia (Li et al, 2012). Furthermore, aged HF-SCs showed increased niche stiffness (Wang et al, 2023), decreased open chromatin landscape and reduced ability to activate genes associated with self-renewal and differentiation (Koester et al, 2021).…”

“…In this study, we present a comprehensive single-cell analysis of the dynamics of the transcriptome and open chromatin landscape in distinct hair follicle lineages with a higher temporal resolution during aging. To facilitate the analysis of cell states at distinct hair cycle stages, we incorporated recently published scRNAseq datasets from postnatal day P38 (P38, catagen) (Zhang et al, 2021), and P53 (telogen) (Wang et al, 2023). Furthermore, we generated new scRNAseq datasets from mice aged 6 months (6 months), 12 months and 24 months.…”