Journal
CELL REPORTS
Volume 35, Issue 10, Pages -Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2021.109225
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Funding
- National Key R&D Program of China [2017YFA0103500, 2017YFA0102800]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA160101XX]
- National Natural Science Foundation of China (NSFC) [31471385, 32070730, 81673104]
- National Thousand Young Talents Award of China
- Shanghai Municipal Science and Technology Major Project [2017SHZDZX01]
- innovative research team of high-level local universities in Shanghai [SSMU-ZDCX20180700]
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This study reveals that miR-24 is an miRNA that regulates the sensitivity of HF progenitors to growth stimuli, impacting hair regeneration. Upregulation of miR-24 leads to reduced responses of HF progenitors to growth cues, while its ablation increases progenitors' growth responsiveness.
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 cellintrinsic mechanism used by HF progenitors to adapt their regenerative competence for different physiological conditions.
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