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

Nature Communications
Daniel L HessGary K Owens

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.

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Citations

Dec 12, 2019·Investigative Ophthalmology & Visual Science·Bruce A CorlissPaul A Yates
Apr 24, 2020·Diabetes·Bruce A CorlissShayn M Peirce
Oct 16, 2020·Arteriosclerosis, Thrombosis, and Vascular Biology·Gamze B BulutGary K Owens
Oct 27, 2020·Frontiers in Cell and Developmental Biology·Hong-Lin LiuQin-Shan Li
Apr 10, 2021·Cellular Oncology (Dordrecht)·Jamal Majidpoor, Keywan Mortezaee
Jun 3, 2021·Journal of Personalized Medicine·Shiyuan Li, Lijun Ding
Oct 8, 2021·Circulation Research·Felicia HartmannJens W Fischer

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Methods Mentioned

BETA
confocal microscopy
RNA-Seq
ChIP-seq
FACS

Software Mentioned

GraphPad Prism
oPOSSUM
Image
ImageJ
Pro Plus
Adobe Illustrator
Zen 2009 Light Edition

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