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.

Perivascular cells are essential to the formation and stabilization of new blood vessels during angiogenesis. Here, Hess and Kelly-Goss et al. show that the stem cell pluripotency factor Oct4 promotes perivascular cell survival and migration required for angiogenesis in contexts of tissue injury and hypoxia.

Details

Title
Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis
Author
Hess, Daniel L 1 ; Kelly-Goss, Molly R 2 ; Cherepanova, Olga A 3 ; Nguyen, Anh T 4 ; Baylis, Richard A 1   VIAFID ORCID Logo  ; Tkachenko Svyatoslav 3 ; Annex, Brian H 5 ; Peirce Shayn M 2 ; Owens, Gary K 6 

1  University of Virginia-School of Medicine, Robert M. Berne Cardiovascular Research Center, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X); University of Virginia-School of Medicine, Department of Biochemistry and Molecular Genetics, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
2  University of Virginia-School of Medicine, Robert M. Berne Cardiovascular Research Center, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X); University of Virginia-School of Medicine, Department of Biomedical Engineering, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
3  Lerner Research Institute, Cleveland, USA (GRID:grid.239578.2) (ISNI:0000 0001 0675 4725) 
4  University of Virginia-School of Medicine, Robert M. Berne Cardiovascular Research Center, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
5  University of Virginia-School of Medicine, Robert M. Berne Cardiovascular Research Center, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X); University of Virginia, Department of Medicine, Cardiovascular Medicine, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
6  University of Virginia-School of Medicine, Robert M. Berne Cardiovascular Research Center, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X); University of Virginia-School of Medicine, Department of Molecular Physiology and Biological Physics, Charlottesville, USA (GRID:grid.27755.32) (ISNI:0000 0000 9136 933X) 
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-08811-z
ProQuest document ID
2186735432
Copyright
This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.