美国加州大学旧金山分校Xin Duan等研究人员合作发现，血管周围神经元通过神经血管接触指导3D血管网格的形成。该研究于2024年5月10日在线发表于国际一流学术期刊《细胞》。
结合小鼠视网膜中的病毒标记、基因标记和单细胞图谱分析，研究人员发现了一种血管周围神经元亚群，被注释为Fam19a4/Nts阳性视网膜神经节细胞（Fam19a4/Nts-RGC），它直接与血管周围的同侧内膜接触。Fam19a4/Nts-RGC的发育消减会导致穿透血管在神经节细胞层（GCL）附近的生长方向失调，从而导致3D血管网格的混乱。研究人员在Fam19a4/Nts-RGC中发现了丰富的PIEZO2表达。
从所有视网膜神经元或Fam19a4/Nts-RGC中缺失Piezo2后，神经血管的直接接触消失了，这表征了Fam19a4/Nts-RGC去除的缺陷。血管结构缺陷导致毛细血管灌注减少，使视网膜对缺血损伤敏感。此外，研究人员还发现了小脑血管形态形成依赖于Piezo2的血管周围颗粒细胞亚群，这表明大脑中的3D血管形态形成依赖于神经元Piezo2。
据介绍，中枢神经系统的血管是一个3D网格，由层状血管床和穿透血管相互连接而成。控制3D网格网络形成的机制在很大程度上仍然未知。
附：英文原文
Title: Perivascular neurons instruct 3D vascular lattice formation via neurovascular contact
Author: Kenichi Toma, Mengya Zhao, Shaobo Zhang, Fei Wang, Hannah K. Graham, Jun Zou, Shweta Modgil, Wenhao H. Shang, Nicole Y. Tsai, Zhishun Cai, Liping Liu, Guiying Hong, Arnold R. Kriegstein, Yang Hu, Jakob Krbelin, Ruobing Zhang, Yaping Joyce Liao, Tyson N. Kim, Xin Ye, Xin Duan
Issue&Volume: 2024-05-10
Abstract: The vasculature of the central nervous system is a 3D lattice composed of laminarvascular beds interconnected by penetrating vessels. The mechanisms controlling 3Dlattice network formation remain largely unknown. Combining viral labeling, geneticmarking, and single-cell profiling in the mouse retina, we discovered a perivascularneuronal subset, annotated as Fam19a4/Nts-positive retinal ganglion cells (Fam19a4/Nts-RGCs),directly contacting the vasculature with perisomatic endfeet. Developmental ablationof Fam19a4/Nts-RGCs led to disoriented growth of penetrating vessels near the ganglioncell layer (GCL), leading to a disorganized 3D vascular lattice. We identified enrichedPIEZO2 expression in Fam19a4/Nts-RGCs. Piezo2 loss from all retinal neurons or Fam19a4/Nts-RGCsabolished the direct neurovascular contacts and phenocopied the Fam19a4/Nts-RGC ablationdeficits. The defective vascular structure led to reduced capillary perfusion andsensitized the retina to ischemic insults. Furthermore, we uncovered a Piezo2-dependentperivascular granule cell subset for cerebellar vascular patterning, indicating neuronalPiezo2-dependent 3D vascular patterning in the brain.
DOI: 10.1016/j.cell.2024.04.010
Source: https://www.cell.com/cell/abstract/S0092-8674(24)00405-7