Research Highlight

This study explores the crucial role of oxygen in early brain development, particularly before the formation of a complete vascular system. The research team used human cerebral organoids (hCOs) as an in vitro model, integrating advanced microscopy techniques and single-cell RNA sequencing (scRNA-seq) to monitor changes in tissue oxygen tension. The results revealed that between weeks 4 and 6, oxygen tension within the hCOs significantly increased, accompanied by metabolic changes and a surge in neurogenesis. Further experiments demonstrated that suppressing this oxygen tension elevation through hypoxia treatment or silencing the Neuroglobin (NGB) gene could hinder organoid development and neuronal differentiation. Through multiomic analysis, the study confirmed that NGB plays a key role in regulating oxygen tension within hCOs. NGB is primarily expressed in excitatory neurons, and its suppression prevents the normal elevation of oxygen tension, leading to impaired organoid development and altered cellular composition. Overall, this research highlights the critical influence of oxygen on early neurodevelopment and provides new insights into the mechanisms of neurodevelopmental disorders and potential therapeutic strategies.