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

First Author  Hess DL Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  967
PubMed ID  30814500 Mgi Jnum  J:276684
Mgi Id  MGI:6287059 Doi  10.1038/s41467-019-08811-z
Citation  Hess DL, et al. (2019) Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis. Nat Commun 10(1):967
abstractText  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.
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