期刊
CELL DEATH AND DIFFERENTIATION
卷 27, 期 3, 页码 949-965出版社
SPRINGERNATURE
DOI: 10.1038/s41418-019-0390-x
关键词
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资金
- National Natural Science Foundation of China [31790412]
- National Science Foundation of China [2015CB943103]
- Ministry of Agriculture Transgenic Major Projects of China [2016ZX08010004]
- Project for Extramural Scientists of State Key Laboratory of Agrobiotechnology [2019SKLAB6-1]
- earmarked fund for Modern Agro-Industry Technology Research Systems of China [CARS-37]
Quiescent satellite cells (SCs) that are activated to produce numerous myoblasts underpin the complete healing of damaged skeletal muscle. How cell-autonomous regulatory mechanisms modulate the balance among cells committed to differentiation and those committed to self-renewal to maintain the stem cell pool remains poorly explored. Here, we show that miR-31 inactivation compromises muscle regeneration in adult mice by impairing the expansion of myoblasts. miR-31 is pivotal for SC proliferation, and its deletion promotes asymmetric cell fate segregation of proliferating cells, resulting in enhanced myogenic commitment and re-entry into quiescence. Further analysis revealed that miR-31 posttranscriptionally suppresses interleukin 34 (IL34) mRNA, the protein product of which activates JAK-STAT3 signaling required for myogenic progression. IL34 inhibition rescues the regenerative deficiency of miR-31 knockout mice. Our results provide evidence that targeting miR-31 or IL34 activities in SCs could be used to counteract the functional exhaustion of SCs in pathological conditions.
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