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Nat Commun. 2019 Feb 27;10(1):967. doi: 10.1038/s41467-019-08811-z.

Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis.

Author information

1
Robert M. Berne Cardiovascular Research Center, University of Virginia-School of Medicine, 415 Lane Road, Suite 1010, Charlottesville, VA, 22908, USA.
2
Department of Biochemistry and Molecular Genetics, University of Virginia-School of Medicine, Charlottesville, VA, 22908, USA.
3
Department of Biomedical Engineering, University of Virginia-School of Medicine, Charlottesville, VA, 22908, USA.
4
Lerner Research Institute, 9500 Euclid Avenue, NB50, Cleveland, OH, 44195, USA.
5
Lerner Research Institute, 9500 Euclid Avenue, JJN3-01, Cleveland, OH, 44195, USA.
6
Department of Medicine, Cardiovascular Medicine, University of Virginia, Charlottesville, VA, 22908, USA.
7
Robert M. Berne Cardiovascular Research Center, University of Virginia-School of Medicine, 415 Lane Road, Suite 1010, Charlottesville, VA, 22908, USA. gko@virginia.edu.
8
Department of Molecular Physiology and Biological Physics, University of Virginia-School of Medicine, Charlottesville, VA, 22908, USA. gko@virginia.edu.

Abstract

The stem cell pluripotency factor Oct4 serves a critical protective role during atherosclerotic plaque development by promoting smooth muscle cell (SMC) investment. Here, we show using Myh11-CreERT2 lineage-tracing with inducible SMC and pericyte (SMC-P) knockout of Oct4 that Oct4 regulates perivascular cell migration and recruitment during angiogenesis. Knockout of Oct4 in perivascular cells significantly impairs perivascular cell migration, increases perivascular cell death, delays endothelial cell migration, and promotes vascular leakage following corneal angiogenic stimulus. Knockout of Oct4 in perivascular cells also impairs perfusion recovery and decreases angiogenesis following hindlimb ischemia. Transcriptomic analyses demonstrate that expression of the migratory gene Slit3 is reduced following loss of Oct4 in cultured SMCs, and in Oct4-deficient perivascular cells in ischemic hindlimb muscle. Together, these results provide evidence that Oct4 plays an essential role within perivascular cells in injury- and hypoxia-induced angiogenesis.

PMID:
30814500
PMCID:
PMC6393549
DOI:
10.1038/s41467-019-08811-z
[Indexed for MEDLINE]
Free PMC Article

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