Activation of the pluripotency factor OCT4 in smooth muscle cells is atheroprotective
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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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The initial stage of VSMC recruitment is, at least in part, Oct4 dependent.
“This initial stage of VSMC recruitment is, at least in part, Oct4 dependent 21 .”
From Vascular smooth muscle cells in atherosclerosis (2019) · cites this paper as [21]
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Self-citation
- Authors
- Cherepanova, O. A., Gomez, D., Shankman, L. S., Swiatlowska, P., Williams, J., Sarmento, O. F., Alencar, G. F., Hess, D. L., Bevard, M. H., Greene, E. S., Murgai, M., Turner, S. D., Geng, Y.-J., Bekiranov, S., Connelly, J. J., Tomilin, A., & Owens, G. K.
- Affiliations
- University of Virginia (US)
- University of Gdańsk (PL)
- Mayo Clinic (US)
- Institute of Cytology (RU)
- Corresponding author
- Owens, Gary K
- ORCID
- Venue
- Nature Medicine
- Published
- 2016-05-16
- Volume
- 22
- Issue
- 6
- Pages
- 657-665
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC4899256
- OpenAlex
- W2400111296
- Cited by
- 221
- References
- 51
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 22 · 2023: 23 · 2022: 25 · 2021: 41 · 2020: 21 · 2019: 25 · 2018: 19 · 2017: 9 · 2016: 4 · 2012: 1
- FWCI
- 11.50
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association (13POST17080043, 11PRE7750030)
- University of Virginia
- National Heart, Lung, and Blood Institute (R01HL038854, R01HL100257, R00HL089412, R01HL087867, R01HL057353, R01HL098538, R01HL121008, T32HL007284)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Keywords
- Oct4, smooth muscle cells, atherosclerosis, atheroprotection, somatic cell reprogramming, embryonic stem cell pluripotency, conditional knockout, ApoE-deficient mice, plaque stability, fibrous cap, necrotic core, intraplaque hemorrhage, HIF1A, KLF4
- MeSH terms
- Kruppel-Like Factor 4, Animals, Aorta, Apolipoproteins E, Cell Movement, Cell Survival, Coronary Artery Disease, Humans, Male, Middle Aged, Blotting, Western, Mutagenesis, Site-Directed, Mice, Knockout, Cell Lineage, Reverse Transcriptase Polymerase Chain Reaction, Myocytes, Smooth Muscle, Chromatin Immunoprecipitation, Atherosclerosis, Octamer Transcription Factor-3, Mice, Kruppel-Like Transcription Factors, Hypoxia-Inducible Factor 1, alpha Subunit, Plaque, Atherosclerotic, Real-Time Polymerase Chain Reaction, Diet, Western
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