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Mechanisms of skin vascular maturation and maintenance captured by longitudinal imaging of live mice
Cell ( IF 45.5 ) Pub Date : 2023-05-10 , DOI: 10.1016/j.cell.2023.04.017
Chen Yuan Kam 1 , Ishani D Singh 1 , David G Gonzalez 1 , Catherine Matte-Martone 1 , Paloma Solá 2 , Guiomar Solanas 2 , Júlia Bonjoch 2 , Edward Marsh 1 , Karen K Hirschi 3 , Valentina Greco 4
Affiliation  

A functional network of blood vessels is essential for organ growth and homeostasis, yet how the vasculature matures and maintains homeostasis remains elusive in live mice. By longitudinally tracking the same neonatal endothelial cells (ECs) over days to weeks, we found that capillary plexus expansion is driven by vessel regression to optimize network perfusion. Neonatal ECs rearrange positions to evenly distribute throughout the developing plexus and become positionally stable in adulthood. Upon local ablation, adult ECs survive through a plasmalemmal self-repair response, while neonatal ECs are predisposed to die. Furthermore, adult ECs reactivate migration to assist vessel repair. Global ablation reveals coordinated maintenance of the adult vascular architecture that allows for eventual network recovery. Lastly, neonatal remodeling and adult maintenance of the skin vascular plexus are orchestrated by temporally restricted, neonatal VEGFR2 signaling. Our work sheds light on fundamental mechanisms that underlie both vascular maturation and adult homeostasis in vivo.



中文翻译:


通过活体小鼠纵向成像捕获皮肤血管成熟和维持的机制



功能性血管网络对于器官生长和体内平衡至关重要,但脉管系统如何成熟并维持体内平衡在活体小鼠中仍然难以捉摸。通过在几天到几周内纵向跟踪相同的新生儿内皮细胞(EC),我们发现毛细血管丛扩张是由血管回归驱动的,以优化网络灌注。新生儿 EC 会重新排列位置,均匀分布在整个发育中的神经丛中,并在成年后变得位置稳定。局部消融后,成人 EC 通过质膜自我修复反应存活,而新生儿 EC 则倾向于死亡。此外,成体 EC 重新激活迁移以协助血管修复。整体消融揭示了成人血管结构的协调维护,从而最终实现网络恢复。最后,皮肤血管丛的新生儿重塑和成人维持是通过暂时受限的新生儿 VEGFR2 信号传导来协调的。我们的工作揭示了血管成熟和成人体内稳态的基本机制。

更新日期:2023-05-10
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