细胞生物学
炎症
组蛋白
先天免疫系统
生物
再生(生物学)
透明质酸
免疫系统
细胞外基质
干细胞
免疫学
生物化学
解剖
基因
作者
Kiran Nakka,Sarah Hachmer,Zeinab Mokhtari,Radmila Kovac,Hina Bandukwala,C. Bernard,Yuefeng Li,Guojia Xie,Chengyu Liu,Magid Fallahi,Lynn A. Megeney,Julien Gondin,Bénédicte Chazaud,Marjorie Brand,Xiaohui Zha,Kai Ge,F. Jeffrey Dilworth
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2022-08-04
卷期号:377 (6606): 666-669
被引量:53
标识
DOI:10.1126/science.abm9735
摘要
Muscle stem cells (MuSCs) reside in a specialized niche that ensures their regenerative capacity. Although we know that innate immune cells infiltrate the niche in response to injury, it remains unclear how MuSCs adapt to this altered environment for initiating repair. Here, we demonstrate that inflammatory cytokine signaling from the regenerative niche impairs the ability of quiescent MuSCs to reenter the cell cycle. The histone H3 lysine 27 (H3K27) demethylase JMJD3, but not UTX, allowed MuSCs to overcome inhibitory inflammation signaling by removing trimethylated H3K27 (H3K27me3) marks at the Has2 locus to initiate production of hyaluronic acid, which in turn established an extracellular matrix competent for integrating signals that direct MuSCs to exit quiescence. Thus, JMJD3-driven hyaluronic acid synthesis plays a proregenerative role that allows MuSC adaptation to inflammation and the initiation of muscle repair.
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