Maintaining a suitable level of sensitivity to environmental cues is crucial for proper function of adult stem cells. Here, we explore how the intrinsic sensitivity of skin hair follicle (HF) progenitors to growth stimuli is dynamically regulated. We discover miR-24 is an miRNA whose expression in HF progenitors inversely correlates with their growth potency in vivo. We show that its upregulation in adult skin epithelium leads to blunted responses of HF progenitors to growth cues and retards hair regeneration, while its conditional ablation leads to hyper-sensitized growth responsiveness of HF progenitors and precocious hair regeneration. Mechanistically, we find that miR-24 limits the intrinsic growth compe... More
Maintaining a suitable level of sensitivity to environmental cues is crucial for proper function of adult stem cells. Here, we explore how the intrinsic sensitivity of skin hair follicle (HF) progenitors to growth stimuli is dynamically regulated. We discover miR-24 is an miRNA whose expression in HF progenitors inversely correlates with their growth potency in vivo. We show that its upregulation in adult skin epithelium leads to blunted responses of HF progenitors to growth cues and retards hair regeneration, while its conditional ablation leads to hyper-sensitized growth responsiveness of HF progenitors and precocious hair regeneration. Mechanistically, we find that miR-24 limits the intrinsic growth competence of HF progenitor by directly targeting Plk3, whose downregulation leads to reduced expression of CCNE1, a key cyclin for cell-cycle entry. These findings reveal an miRNA-mediated dynamic and cell-intrinsic mechanism used by HF progenitors to adapt their regenerative competence for different physiological conditions.
