Activation of the Pluripotency Factor OCT4 in Smooth Muscle Cells is Atheroprotective

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2016 May 17

PMID 27183216

Citations 125

Authors

Olga A Cherepanova

Delphine Gomez

Laura S Shankman

Pamela Swiatlowska

Jason Williams

Olga F Sarmento

Gabriel F Alencar

Daniel L Hess

Melissa H Bevard

Elizabeth S Greene

Meera Murgai

Stephen D Turner

Yong-Jian Geng

Stefan Bekiranov

Jessica J Connelly

Alexey Tomilin

Gary K Owens

Affiliations

Soon will be listed here.

Abstract

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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