Fate decision of satellite cell differentiation and self-renewal by miR31-IL34 axis
Fate decision of satellite cell differentiation and self-renewal by miR31-IL34 axis
复制标题
DOI：
10.1038/s41418-019-0390-x
复制
发表时间：
2020-03-01
影响因子：
12.4
通讯作者：
Meng, Qingyong
中科院分区：
文献类型：
--
作者：
Su, Yang;Yu, Yingying;Meng, Qingyong
静止的卫星细胞（SC）被激活后产生大量成肌细胞，为受损骨骼肌的完全愈合奠定基础。细胞自主调节机制如何调节致力于分化的细胞和那些致力于自我更新以维持干细胞库的细胞之间的平衡仍然鲜为人知。在这里，我们发现 miR-31 失活通过损害成肌细胞的扩张来损害成年小鼠的肌肉再生。 miR-31 对于 SC 增殖至关重要，其缺失会促进增殖细胞的不对称细胞命运分离，从而增强肌源性承诺并重新进入静止状态。进一步分析显示，miR-31 转录后抑制白细胞介素 34 (IL34) mRNA，其蛋白质产物激活肌原性进展所需的 JAK-STAT3 信号传导。 IL34 抑制可挽救 miR-31 敲除小鼠的再生缺陷。我们的结果提供了证据，表明针对 SC 中的 miR-31 或 IL34 活性可用于抵消病理条件下 SC 的功能衰竭。
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.