Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero.
Isolation and function of mouse tissue resident vascular precursors marked by myelin protein zero.
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DOI：
10.1084/jem.20102187
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发表时间：
2011-05-09
期刊：
影响因子：
--
通讯作者：
Suda T
中科院分区：
文献类型：
--
作者：
Kubota Y;Takubo K;Hirashima M;Nagoshi N;Kishi K;Okuno Y;Nakamura-Ishizu A;Sano K;Murakami M;Ema M;Omatsu Y;Takahashi S;Nagasawa T;Shibuya M;Okano H;Suda T
新鉴定的组织驻留血管前体细胞被招募到生长的血管中，并有助于成年小鼠的血管发生。血管发生描述了血管前体细胞从头血管形成的过程。虽然形成的第一个主要的血管，如背主动脉和主静脉，发生在胚胎血管发生，前体细胞群体的贡献，出生后的血管发育还没有得到很好的理解。在这里，我们确定了一个新的人口出生后的血管前体细胞的小鼠。这些细胞表达许旺细胞蛋白髓鞘蛋白零（Po），并表现出CD 45 − CD 31 −VEcad−c-kit+ CXCR 4+表面表型。Po+血管前体（PVP）被募集到生长的血管系统中，并且在成年小鼠中包含少量动脉内皮细胞群体。PVP向生长血管中的募集由CXCL 12-CXCR 4信号传导介导，并且在Notch抑制诱导的血管扩张期间增强。Flk 1（VEGF受体）的PO特异性消融导致视网膜中的分支缺陷和动脉图案化不足，以及肿瘤和缺血组织的新血管形成减少。因此，在出生后的小鼠中，尽管生长的血管主要是通过先前存在的血管的血管生成形成的，但少数动脉内皮细胞可能来源于组织驻留的血管前体细胞。
Newly identified tissue-resident vascular precursor cells are recruited into growing vessels and contribute to vasculogenesis in adult mice. Vasculogenesis describes the process of de novo vessel formation from vascular precursor cells. Although formation of the first major vessels, such as the dorsal aorta and cardinal veins, occurs during embryonic vasculogenesis, the contribution of precursor cell populations to postnatal vessel development is not well understood. Here, we identified a novel population of postnatal vascular precursor cells in mice. These cells express the Schwann cell protein myelin protein zero (Po) and exhibit a CD45−CD31−VEcad−c-kit+CXCR4+ surface phenotype. Po+ vascular precursors (PVPs) are recruited into the growing vasculature, and comprise a minor population of arterial endothelial cells in adult mice. Recruitment of PVPs into growing vessels is mediated by CXCL12–CXCR4 signaling, and is enhanced during vascular expansion induced by Notch inhibition. Po-specific ablation of Flk1, a receptor for VEGF, results in branching defects and insufficient arterial patterning in the retina, as well as reduced neovascularization of tumors and ischemic tissues. Thus, in postnatal mice, although growing vessels are formed primarily by angiogenesis from preexisting vessels, a minor population of arterial endothelia may be derived from tissue-resident vascular precursor cells.
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