Fate decision of satellite cell differentiation and self-renewal by miR-31-IL34 axis

Autor: Su, Yang, Yu, Yingying, Liu, Chuncheng, Zhang, Yuying, Liu, Chang, Ge, Mengxu, Li, Lei, Lan, Miaomiao, Wang, Tongtong, Li, Min, Liu, Fan, Xiong, Lei, Wang, Kun, He, Ting, Shi, Jianyun, Song, Yongli, Zhao, Yaofeng, Li, Ning, Yu, Zhengquan, Meng, Qingyong
Zdroj: Cell Death and Differentiation; March 2020, Vol. 27 Issue: 3 p949-965, 17p
Abstrakt: 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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