KLF4公司
体细胞
胚胎干细胞
生物
细胞生物学
病变
心肌细胞
解剖
病理
诱导多能干细胞
医学
遗传学
基因
作者
Olga A. Cherepanova,Delphine Gomez,Laura S. Shankman,Pamela Swiatlowska,Jason Williams,Olga F. Sarmento,Gabriel F. Alencar,Daniel Heß,Melissa Bevard,Elizabeth S. Greene,Meera Murgai,Stephen D. Turner,Yong‐Jian Geng,Stefan Bekiranov,Jessica J. Connelly,Alexey Tomilin,Gary K. Owens
出处
期刊:Nature Medicine
[Springer Nature]
日期:2016-05-16
卷期号:22 (6): 657-665
被引量:164
摘要
The pluripotency factor OCT4 is expressed in smooth muscle cells of atherosclerotic lesions in both mice and humans, and has atheroprotective effects in mice. Although somatic cell activation of the embryonic stem cell (ESC) pluripotency factor OCT4 has been reported, this previous work has been controversial and has not demonstrated a functional role for OCT4 in somatic cells. Here we demonstrate that smooth muscle cell (SMC)-specific conditional knockout of Oct4 in Apoe−/− mice resulted in increased lesion size and changes in lesion composition that are consistent with decreased plaque stability, including a thinner fibrous cap, increased necrotic core area, and increased intraplaque hemorrhage. Results of SMC-lineage-tracing studies showed that these effects were probably the result of marked reductions in SMC numbers within lesions and SMC investment within the fibrous cap, which may result from impaired SMC migration. The reactivation of Oct4 within SMCs was associated with hydroxymethylation of the Oct4 promoter and was hypoxia inducible factor-1α (HIF-1α, encoded by HIF1A) and Krüppel-like factor-4 (KLF4)-dependent. These results provide the first direct evidence that OCT4 has a functional role in somatic cells, and they highlight the potential role of OCT4 in normal and diseased somatic cells.
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