State Key Laboratories for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Yuanmingyuan West Road No. 2, Haidian District, Beijing, 100193, China.
The Institute of Bioengineering and Technology, Inner Mongolia University of Science and Technology, Baotou, 014010, China.
Cell Death Differ. 2020 Mar;27(3):949-965. doi: 10.1038/s41418-019-0390-x. Epub 2019 Jul 22.
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.
静息卫星细胞 (SCs) 在受到刺激后会产生大量成肌细胞，从而为受损骨骼肌的完全修复提供支持。细胞自主调节机制如何在分化细胞、自我更新细胞之间的平衡中发挥作用，以维持干细胞库，这方面的研究仍不够充分。本文中，我们发现 miR-31 的失活通过损害成肌细胞的扩增而损害成年小鼠的肌肉再生。miR-31 对 SC 的增殖至关重要，其缺失促进了增殖细胞的不对称细胞命运分离，从而增强了成肌细胞的分化和重新进入静息状态。进一步的分析表明，miR-31 转录后抑制白细胞介素 34 (IL34) mRNA，其蛋白产物激活 JAK-STAT3 信号通路，该信号通路是成肌进展所必需的。抑制 IL34 可挽救 miR-31 敲除小鼠的再生缺陷。我们的研究结果为靶向 SC 中的 miR-31 或 IL34 活性以对抗病理条件下 SC 功能衰竭提供了证据。
