胶质发生
神经发生
细胞生物学
生物
祖细胞
神经干细胞
新皮层
星形胶质细胞
血管生成
神经科学
内皮干细胞
基因敲除
内皮
室下区
神经球
干细胞
中枢神经系统
细胞培养
成体干细胞
内分泌学
生物化学
遗传学
体外
作者
Wenwen Wang,Lihe Su,Yanyan Wang,Chenxiao Li,Fen Ji,Jianwei Jiao
标识
DOI:10.1002/advs.202105208
摘要
During mammalian cortical development, neural stem/progenitor cells (NSCs) gradually alter their characteristics, and the timing of generation of neurons and glial cells is strictly regulated by internal and external factors. However, whether the blood vessels located near NSCs affect the neurogenic-to-gliogenic transition remain unknown. Here, it is demonstrated that endothelial uncoupling protein 2 (UCP2) deletion reduces blood vessel diameter and affects the transition timing of neurogenesis and gliogenesis. Deletion of endothelial UCP2 results in a persistent increase in astrocyte production at the postnatal stage. Mechanistically, the endothelial UCP2/ROS/ERK1/2 pathway increases chymase-1 expression to enhance angiotensin II (AngII) secretion outside the brain endothelium. The endotheliocyte-driven AngII-gp130-JAK-STAT pathway also regulates gliogenesis initiation. Moreover, endothelial UCP2 knockdown decreases human neural precursor cell (hNPC) differentiation into neurons and accelerates hNPC differentiation into astrocytes. Altogether, this work provides mechanistic insights into how endothelial UCP2 regulates the neurogenic-to-gliogenic fate switch in the developing neocortex.
科研通智能强力驱动
Strongly Powered by AbleSci AI