Department of Genetics, Yale School of Medicine, New Haven, CT 06510, USA.
Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, 08028 Barcelona, Spain.
Cell. 2023 May 25;186(11):2345-2360.e16. doi: 10.1016/j.cell.2023.04.017. Epub 2023 May 10.
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.
血管的功能网络对于器官的生长和稳态至关重要，但血管如何成熟并维持稳态在活体小鼠中仍然难以捉摸。通过对相同的新生内皮细胞（EC）进行数天到数周的纵向追踪，我们发现毛细血管丛的扩张是由血管退化驱动的，以优化网络灌注。新生 EC 重新排列位置，均匀分布在整个发育中的丛中，并在成年后保持位置稳定。局部消融后，成年 EC 通过质膜自我修复反应存活，而新生 EC 则容易死亡。此外，成年 EC 会重新激活迁移以协助血管修复。全局消融揭示了协调的成年血管结构维持，这允许最终的网络恢复。最后，皮肤血管丛的新生重塑和成年维持由时间限制的、新生的 VEGFR2 信号协调。我们的工作揭示了基础机制，这些机制不仅存在于血管成熟中，也存在于体内的成年稳态中。
