4.8 Article

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

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.2220635120

Keywords

cell mechanics; actomyosin contractility; hair follicle stem cells; hair regeneration; miRNA

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This study reveals that hair follicle stem cells (SCs) and hair germ (HG) progenitors have different mechanical properties, with SCs being stiff and resistant to size change, while HG progenitors are soft and periodically enlarge and contract. During hair follicle growth, HGs reduce contraction and more frequently enlarge, which is associated with weakening of the actomyosin network and nuclear YAP accumulation. miR-205 can reduce actomyosin contractility and activate hair regeneration in mice.
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 modulate their size and function remains unclear. Here, 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 of hair follicle growth, HGs reduce contraction and more frequently enlarge, a process that is associated with weakening of the actomyosin network, nuclear YAP accumulation, and cell cycle reentry. Induction of miR-205, a novel regulator of the actomyosin cytoskeleton, reduces actomyosin contractility 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.

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