Pericytes are critical for microvascular stability and maintenance, among other important physiological functions, yet their involvement in vessel formation processes remains poorly understood. To gain insight into pericyte behaviors during vascular remodeling, we developed two complementary tissue explant models utilizing ‘double reporter’ animals with fluorescently-labeled pericytes and endothelial cells (via Ng2:DsRed and Flk-1:eGFP genes, respectively). Time-lapse confocal imaging of active vessel remodeling within adult connective tissues and embryonic skin revealed a subset of pericytes detaching and migrating away from the vessel wall. Vessel-associated pericytes displayed rapid filopodial sampling near sprouting endothelial cells that emerged from parent vessels to form nascent branches. Pericytes near angiogenic sprouts were also more migratory, initiating persistent and directional movement along newly forming vessels. Pericyte cell divisions coincided more frequently with elongating endothelial sprouts, rather than sprout initiation sites, an observation confirmed with in vivo data from the developing mouse brain. Taken together, these data suggest that (i) pericyte detachment from the vessel wall may represent an important physiological process to enhance endothelial cell plasticity during vascular remodeling, and (ii) pericyte migration and proliferation are highly synchronized with endothelial cell behaviors during the coordinated expansion of a vascular network.

中文翻译：

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周细胞迁移和增殖与内皮细胞发芽动力学紧密同步

周细胞对于微血管的稳定性和维持以及其他重要的生理功能至关重要，但它们在血管形成过程中的参与仍然知之甚少。为了深入了解血管重塑过程中的周细胞行为，我们开发了两个互补的组织外植体模型，利用具有荧光标记的周细胞和内皮细胞的“双重报告”动物（通过Ng2:DsRed和Flk-1:eGFP基因，分别）。成人结缔组织和胚胎皮肤内活动血管重塑的延时共聚焦成像显示，一部分周细胞从血管壁分离和迁移。与血管相关的周细胞在从母体血管出现以形成新生分支的发芽内皮细胞附近显示出快速的丝状足取样。血管生成芽附近的周细胞也更具迁移性，沿着新形成的血管开始持续和定向运动。周细胞分裂更频繁地与伸长的内皮芽同时发生，而不是芽起始位点，这一观察结果在体内得到证实来自发育中的小鼠大脑的数据。总之，这些数据表明（i）周细胞从血管壁上脱离可能是在血管重塑过程中增强内皮细胞可塑性的重要生理过程，以及（ii）周细胞迁移和增殖与协调扩张过程中的内皮细胞行为高度同步的血管网络。