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.

中文翻译：

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JMJD3 激活的透明质酸合成在炎症环境中驱动肌肉再生

肌肉干细胞 (MuSC) 位于确保其再生能力的特殊生态位中。虽然我们知道先天免疫细胞会渗入生态位以应对损伤，但尚不清楚肌肉干细胞如何适应这种改变的环境以启动修复。在这里，我们证明来自再生生态位的炎性细胞因子信号会损害静止 MuSC 重新进入细胞周期的能力。组蛋白 H3 赖氨酸 27 (H3K27) 去甲基化酶 JMJD3，但不是 UTX，允许 MuSC 通过去除三甲基化的 H3K27 (H3K27me3) 标记来克服抑制性炎症信号传导。有2位点启动透明质酸的产生，进而建立了一种细胞外基质，能够整合指导 MuSC 退出静止状态的信号。因此，JMJD3 驱动的透明质酸合成发挥促再生作用，使 MuSC 适应炎症和启动肌肉修复。