Endothelial Cells Mediated by UCP2 Control the Neurogenic‐to‐Astrogenic Neural Stem Cells Fate Switch During Brain Development

• Published in: Advanced science Vol. 9; no. 18; pp. e2105208 - n/a
• Main Authors: Wang, Wenwen, Su, Libo, Wang, Yanyan, Li, Chenxiao, Ji, Fen, Jiao, Jianwei
• Format: Journal Article
• Language: English
• Published: Germany John Wiley & Sons, Inc 01.06.2022; John Wiley and Sons Inc; Wiley
• Subjects: Blood vessels; cortical development; endothelial UCP2; Localization; Metabolism; Morphology; Nervous system; Neurogenesis; neurogenic‐to‐astrogenic fate switch; Neurons; cortical development; endothelial UCP2; neurogenic-to-astrogenic fate switch
• ISSN: 2198-3844; 2198-3844
• DOI: 10.1002/advs.202105208

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. Blood vessels reside in close physical proximity to the neural precursor cell (NPC) domains. Endothelial derived signals on NPCs regulate the timing of the neurogenic‐to‐astrocyte fate switch, resulting in an increase in the number of astrocytes in the developing neocortex. This work provides new insights into the regulatory link between blood vessels and sequential differentiation of NPCs.