Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective
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 con...
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Published in | Nature medicine Vol. 22; no. 6; pp. 657 - 665 |
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Main Authors | , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
London
Nature Publishing Group UK
01.06.2016
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | 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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1078-8956 1546-170X |
DOI: | 10.1038/nm.4109 |