Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective.
Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective.
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DOI：
10.1038/nm.4109
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发表时间：
2016-06
期刊：
影响因子：
82.9
通讯作者：
Owens GK
中科院分区：
文献类型：
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作者：
Cherepanova OA;Gomez D;Shankman LS;Swiatlowska P;Williams J;Sarmento OF;Alencar GF;Hess DL;Bevard MH;Greene ES;Murgai M;Turner SD;Geng YJ;Bekiranov S;Connelly JJ;Tomilin A;Owens GK
有争议的说法是胚胎干细胞（ESC）多能性因子OCT 4在体细胞中被激活，但没有证据表明它在这些细胞中起作用。在本文中，我们证明了Apoe−/−小鼠中的平滑肌细胞（SMC）特异性条件性敲除Oct 4导致病变大小增加和与斑块稳定性降低一致的变化，包括更薄的纤维帽，坏死核心增加和斑块内出血增加。SMC谱系追踪研究的结果表明，这些变化可能是由于病变内SMC数量显著减少，包括纤维帽内SMC迁移和投资受损。SMC内Oct 4的再激活与Oct 4启动子的羟甲基化相关，并且是HIF 1 α和KLF 4依赖性的。结果提供了第一个直接证据，表明OCT 4在体细胞中起着功能性作用，并强调了进一步研究OCT 4在正常和患病体细胞中可能功能的重要性。
There are controversial claims that the embryonic stem cell (ESC) pluripotency factor OCT4 is activated in somatic cells, but there is no evidence it plays a functional role in these cells. Herein we demonstrate that smooth muscle cell (SMC)-specific conditional knockout of Oct4 within Apoe−/− mice resulted in increased lesion size and changes consistent with decreased plaque stability including a thinner fibrous cap, increased necrotic core, and increased intra-plaque hemorrhage. Results of SMC-lineage tracing studies showed that these changes were likely due to marked reductions in SMC number within lesions including impaired SMC migration and investment within the fibrous cap. Re-activation of Oct4 within SMCs was associated with hydroxymethylation of the Oct4 promoter and was HIF1α- and KLF4-dependent. Results provide the first direct evidence that OCT4 plays a functional role in somatic cells and highlight the importance of further investigation of possible OCT4 functions in normal and diseased somatic cells.