Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis
Perivascular cell-specific knockout of the stem cell pluripotency gene Oct4 inhibits angiogenesis
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DOI：
10.1038/s41467-019-08811-z
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发表时间：
2019-02-27
影响因子：
16.6
通讯作者：
Owens, Gary K.
中科院分区：
文献类型：
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作者：
Hess, Daniel L.;Kelly-Goss, Molly R.;Owens, Gary K.
干细胞多能性因子Oct 4通过促进平滑肌细胞（SMC）的投资，在动脉粥样硬化斑块的发展过程中发挥关键的保护作用。在这里，我们使用Myh 11-CreERT 2谱系追踪与诱导型SMC和周细胞（SMC-P）敲除Oct 4，Oct 4调节血管生成过程中血管周围细胞的迁移和招募。敲除血管周围细胞中的Oct 4显著损害血管周围细胞迁移，增加血管周围细胞死亡，延迟内皮细胞迁移，并促进角膜血管生成刺激后的血管渗漏。敲除血管周围细胞中的Oct 4也损害灌注恢复并减少后肢缺血后的血管生成。转录组学分析表明，迁移基因Slit 3的表达减少后，损失的Oct 4在培养的SMC，和Oct 4缺陷血管周围细胞缺血后肢肌肉。总之，这些结果提供了证据，表明Oct 4在血管周围细胞中在损伤和缺氧诱导的血管生成中起着重要作用。
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.