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

Daniel L. Hess, Molly R. Kelly-Goss, Olga A. Cherepanova, Anh T. Nguyen, Richard A. Baylis, Svyatoslav Tkachenko, Brian H. Annex, Shayn M. Peirce, Gary K. Owens

Research output: Contribution to journalArticle

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-CreER T2 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.

Original languageEnglish (US)
Article number967
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019
Externally publishedYes

Fingerprint

angiogenesis
stem cells
Stem cells
genes
Muscle
Stem Cells
Genes
Cell Movement
Hindlimb
cells
Smooth Muscle Myocytes
smooth muscle
muscle cells
Endothelial cells
Cell death
Pericytes
Stem Cell Factor
Atherosclerotic Plaques
Cells
Blood Vessels

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Hess, D. L., Kelly-Goss, M. R., Cherepanova, O. A., Nguyen, A. T., Baylis, R. A., Tkachenko, S., ... Owens, G. K. (2019). Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis. Nature communications, 10(1), [967]. https://doi.org/10.1038/s41467-019-08811-z

Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis. / Hess, Daniel L.; Kelly-Goss, Molly R.; Cherepanova, Olga A.; Nguyen, Anh T.; Baylis, Richard A.; Tkachenko, Svyatoslav; Annex, Brian H.; Peirce, Shayn M.; Owens, Gary K.

In: Nature communications, Vol. 10, No. 1, 967, 01.12.2019.

Research output: Contribution to journalArticle

Hess, DL, Kelly-Goss, MR, Cherepanova, OA, Nguyen, AT, Baylis, RA, Tkachenko, S, Annex, BH, Peirce, SM & Owens, GK 2019, 'Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis', Nature communications, vol. 10, no. 1, 967. https://doi.org/10.1038/s41467-019-08811-z
Hess DL, Kelly-Goss MR, Cherepanova OA, Nguyen AT, Baylis RA, Tkachenko S et al. Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis. Nature communications. 2019 Dec 1;10(1). 967. https://doi.org/10.1038/s41467-019-08811-z
Hess, Daniel L. ; Kelly-Goss, Molly R. ; Cherepanova, Olga A. ; Nguyen, Anh T. ; Baylis, Richard A. ; Tkachenko, Svyatoslav ; Annex, Brian H. ; Peirce, Shayn M. ; Owens, Gary K. / Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis. In: Nature communications. 2019 ; Vol. 10, No. 1.
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