Pericyte Progenitor Coupling to the Emerging Endothelium During Vasculogenesis via Connexin 43.
Pericyte Progenitor Coupling to the Emerging Endothelium During Vasculogenesis via Connexin 43.
复制标题
血管生成过程中周细胞祖细胞通过连接蛋白 43 与新生内皮细胞偶联。
DOI：
10.1161/atvbaha.121.317324
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Chappell JC
中科院分区：
文献类型：
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作者：
Payne LB;Tewari BP;Dunkenberger L;Bond S;Savelli A;Darden J;Zhao H;Willi C;Kanodia R;Gude R;Powell MD;Oestreich KJ;Sontheimer H;Dal-Pra S;Chappell JC
血管周细胞（PC）稳定血管并促进其成熟，同时在微血管功能中发挥其他关键作用。然而，相对较少的是知道他们的前体参与血管发育的最早阶段，特别是在vasculogenesis。我们结合了高功率，延时成像与新兴的PC和内皮细胞（EC）在报告小鼠和细胞系的转录谱。我们还分析了Ng 2+细胞内Cx43/Gja 1表达缺陷的条件转基因动物。Ng 2-DsRed+细胞的一个子集，可能是PC/壁细胞前体，与EC分化和组织一起出现，并在体内和体外物理参与血管生成内皮。我们发现，这一群体的分化PC/壁祖细胞和其他谱系，包括血管生成和神经元/神经胶质细胞类型之间没有重叠。我们还观察到细胞-细胞偶联，并确定了基于连接蛋白43（Cx43）的间隙连接，有助于血管组装过程中的PC-EC前体通讯。Ng 2 + PC祖细胞中Cx43/Gja 1的遗传缺失损害了动物亚组中的胚胎血管形成，而存活的突变体显示很少或没有血管异常，表明Ng 2+细胞中Cx43/Gja 1缺失的弹性或额外连接蛋白亚型的潜在补偿。总之，我们的数据表明，一个独特的PC谱系出现在血管发生旁边，并在早期血管形成过程中通过Cx43与新生内皮直接沟通。PC/壁细胞祖细胞中的Cx43/Gja 1缺失可诱导胚胎血管畸形发生，但替代连接蛋白亚型可能能够补偿。这些数据提供了可能重塑当前血管发育框架的见解，也可能为组织再血管化/血管化策略提供信息。
Vascular pericytes (PCs) stabilize blood vessels and contribute to their maturation, while playing other key roles in microvascular function. Nevertheless, relatively little is known about involvement of their precursors in the earliest stages of vascular development, specifically during vasculogenesis. We combined high-power, time-lapse imaging with transcriptional profiling of emerging PCs and endothelial cells (ECs) in reporter mouse and cell lines. We also analyzed conditional transgenic animals deficient in Cx43/Gja1 expression within Ng2+ cells. A subset of Ng2-DsRed+ cells, likely PC/mural cell precursors, arose alongside EC differentiation and organization, and physically engaged vasculogenic endothelium in vivo and in vitro. We found no overlap between this population of differentiating PC/mural progenitors and other lineages including hemangiogenic and neuronal/glial cell types. We also observed cell-cell coupling and identified Connexin43 (Cx43)-based gap junctions contributing to PC-EC precursor communication during vascular assembly. Genetic loss of Cx43/Gja1 in Ng2+ PC progenitors compromised embryonic blood vessel formation in a subset of animals, while surviving mutants displayed little to no vessel abnormalities, suggesting a resilience to Cx43/Gja1 loss in Ng2+ cells or potential compensation by additional connexin isoforms. Together, our data suggest that a distinct PC lineage emerges alongside vasculogenesis and directly communicates with the nascent endothelium via Cx43 during early vessel formation. Cx43/Gja1 loss in PC/mural cell progenitors can induce embryonic vessel dysmorphogenesis, but alternate connexin isoforms may be able to compensate. These data provide insight that may reshape the current framework of vascular development and may also inform tissue re-/vascularization strategies.
DOI：
10.1111/micc.12461
发表时间：
2018-07
期刊：
Microcirculation (New York, N.Y. : 1994)
影响因子：
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作者：
Zhao H;Darden J;Chappell JC
通讯作者：
Chappell JC