HDAC4 promotes Pax7-dependent satellite cell activation and muscle regeneration
HDAC4 promotes Pax7-dependent satellite cell activation and muscle regeneration
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DOI：
10.15252/embr.201439195
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发表时间：
2014-11-01
期刊：
影响因子：
7.7
通讯作者：
Yao, Tso-Pang
中科院分区：
文献类型：
--
作者：
Choi, Moon-Chang;Ryu, Soyoung;Yao, Tso-Pang
在肌肉再生过程中，转录因子Pax7刺激卫星细胞(SCs)向肌肉分化，但限制脂肪的生成。在这里，我们认为HDAC4是依赖Pax7的肌肉再生的调节因子。在HDAC4缺陷的干细胞中，Pax7及其靶基因的表达减少。我们发现HDAC4调控的Lix1基因是干细胞增殖所必需的Pax7靶基因。HDAC4失活会导致SC增殖缺陷、肌肉再生和异常脂肪堆积。此外，棕色脂肪主调控子Prdm16及其抑制的microRNA-133的表达也被解除调控。因此，HDAC4是一种新的依赖于Pax7的SC增殖和再生肌肉中潜在的命运决定的调节因子。
During muscle regeneration, the transcription factor Pax7 stimulates the differentiation of satellite cells (SCs) toward the muscle lineage but restricts adipogenesis. Here, we identify HDAC4 as a regulator of Pax7-dependent muscle regeneration. In HDAC4-deficient SCs, the expression of Pax7 and its target genes is reduced. We identify HDAC4-regulated Lix1 as a Pax7 target gene required for SC proliferation. HDAC4 inactivation leads to defective SC proliferation, muscle regeneration, and aberrant lipid accumulation. Further, expression of the brown adipose master regulator Prdm16 and its inhibitory microRNA-133 are also deregulated. Thus, HDAC4 is a novel regulator of Pax7-dependent SC proliferation and potentially fate determination in regenerating muscle.