Stiffness and actomyosin contractility are intrinsic mechanical properties of animal cells required for the shaping of tissues. However, whether tissue stem cells and progenitors located within stem cell niche have different mechanical properties that modulate their size and function remains unclear. In this study, published in PNAS, the investigators determined spatiotemporal compartmentalization of mechanical properties and their associated cell activities within the hair germ-stem cell niche during quiescence and activation. They showed that hair follicle stem cells in the bulge are stiff with high actomyosin contractility and resistant to size change, whereas hair germ progenitors are soft and periodically enlarge and contract during quiescence. During activation of hair follicle growth, hair germs reduce contraction and more frequently enlarge, a process that is associated with weakening of the actomyosin network, nuclear YAP accumulation, and cell cycle reentry. The authors have identified a tiny RNA, microR-205, a versatile and potent regulator of the actin cytoskeleton, whose expression modulates actomyosin contractility and the dynamics of cell size changes. This study was conducted in genetically engineered mouse models. The scientists used advanced microscopy tools, including atomic force microscopy, to measure the stiffness and two-photon microscopy to monitor cell behaviors in live animals. When the stem cells were genetically manipulated to produce more miR-205, they promoted hair growth in young and old mice in 10 days.
The study demonstrated the possibility of stimulating hair growth tissue regeneration by fine-tuning cell mechanics. Because of the potential to deliver microRNA by nanoparticles directly into the skin, the team plan, as next step, to test whether topically delivered miR-205 can stimulate hair growth first in mice and then, if successful, to design experiments in humans.