Pericyte migration and proliferation are tightly synchronized to endothelial cell sprouting dynamics
Pericyte migration and proliferation are tightly synchronized to endothelial cell sprouting dynamics
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DOI：
10.1093/intbio/zyaa027
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发表时间：
2021-01-30
影响因子：
2.5
通讯作者：
Chappell, John C.
中科院分区：
文献类型：
--
作者：
Payne, Laura Beth;Darden, Jordan;Chappell, John C.
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期间的周细胞行为，我们开发了两种互补的组织外植体模型，利用具有荧光标记周细胞和内皮细胞的“双报告基因”动物（分别通过Ng 2：DsRed和Flk-1：eGFP基因）。成人结缔组织和胚胎皮肤内活跃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并迁移。血管相关的周细胞显示快速丝状伪足采样附近的萌芽内皮细胞出现从母血管形成新生的分支。血管新生芽附近的周细胞也更具有迁移性，开始沿着沿着新形成的血管进行持续和定向的运动。周细胞分裂更频繁地与伸长的内皮芽相吻合，而不是芽起始位点，这一观察结果得到了发育中小鼠大脑的体内数据的证实。总之，这些数据表明：（i）周细胞从血管壁脱离可能代表了血管重塑期间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血管网络协调扩张期间的内皮细胞行为高度同步。
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.