|Yang Su,Lei Xiong,Kun Wang,Ting He,Jianyun Shi,Yongli Song,Yaofeng Zhao,Ning Li,Zhengquan Yu,Qingyong Meng.Fate Decision of Satellite Cell Differentiation and Self-Renewal by miR-31-IL34 Axis.DOI: 10.1038/s41418-019-0390-x|
Fate Decision of Satellite Cell Differentiation and Self-Renewal by miR-31-IL34 Axis
Yang Su,Yingying Yu,Chuncheng Liu,Yuying Zhang,Chang Liu,Mengxu G,Lei Li,Miaomiao Lan,Tongtong Wang,Min Li,Fan Liu,Lei Xiong,Kun Wang,Ting He,Jianyun Shi,Yongli Song,Yaofeng Zhao,Ning Li,Zhengquan Yu,Qingyong Meng
Cell Death And Differentiation
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.