Academia Sinica Logo

A research team led by Dr. Yi-Chung Tung at the Research Center for Applied Sciences, Academia Sinica, has uncovered the critical role of oxygen tension in early brain development, particularly its influence on neurogenesis before the brain’s vascular system is fully established. Using human brain organoids as a model, the team applied fluorescence lifetime imaging microscopy (FLIM) combined with oxygen-sensing microbeads to monitor real-time changes in oxygen tension within the organoids. Through single-cell RNA sequencing and metabolomic analysis, they investigated how oxygen tension affects developmental progression. The results showed that between weeks 4 and 6 of development, oxygen tension within the organoids significantly increased, promoting energy metabolism regulation and neuronal generation. Further experiments revealed that lowering oxygen tension or inhibiting neuroglobin expression suppressed this increase in oxygen levels, thereby affecting organoid development and reducing neuronal production. This study is the first to demonstrate the pivotal influence of oxygen tension variation during specific developmental stages on brain development. It provides new insights into the mechanisms of neurodegenerative diseases and potential therapeutic strategies.

The research has been published on March 12, 2025 in Science Advances. The first author is Dr. Yuan-Hsuan Liu, a postdoctoral researcher at the Research Center for Applied Sciences, Academia Sinica, in collaboration with Dr. Hsiao-Mei Wu at the Department of Biomechatronics Engineering, National Taiwan University. The research was supported by the Academia Sinica Career Development Award, Neuroscience Core Facility, and the National Science and Technology Council.