Shaping early neural development by timed elevated tissue oxygen tension: Insights from multiomic analysis on human cerebral organoids

Oxygen plays a critical role in early neural development in brains, particularly before establishment of complete vasculature; however, it has seldom been investigated due to technical limitations. This study uses an in vitro human cerebral organoid model with multiomic analysis, integrating advanced microscopies and single-cell RNA sequencing, to monitor tissue oxygen tension during neural development. Results reveal a key period between weeks 4 and 6 with elevated intra-organoid oxygen tension, altered energy homeostasis, and rapid neurogenesis within the organoids. The timed oxygen tension elevation can be suppressed by hypoxia treatment or silencing of neuroglobin gene. This study provides insights into the role of oxygen in early neurogenesis from functional, genotypic, phenotypic, and proteomic aspects. These findings highlight the significance of the timed tissue oxygen tension elevation in neurogenesis and provide insights into the role of neuroglobin in neural development, with potential implications for understanding neurodegenerative diseases and therapeutic strategies.