Embryonic stem (ES) cell maintenance and differentiation are dynamic processes controlled by various intrinsic and extrinsic factors. Identifying these factors will enhance the understanding about developmental process and improve the application of stem cells in clinic. Previous studies highlight a shift between non-oxidative and oxidative energy metabolism to play roles during differentiation. Oxidative metabolism is a major source of reactive oxygen species (ROS) which is regulated by a cytoprotective transcription factor, Nuclear factor erythroid 2-related factor 2 (Nrf2). Therefore, this study investigate relationship between metabolism, ROS, and Nrf2 during mouse ES cell differentiation. In vitro models representing early lineage differentiation were used. By measuring metabolic profiles, ROS, and Nrf2 levels from the models, Nrf2 was found related to pluripotency and ROS. However, relationship among metabolism and Nrf2 or ROS could not be detected. Gain- and loss-of-function experiments by pharmacological activator, short hairpin RNA knockdown, and CRISPR-Cas9 genome editing showed that Nrf2 could promote pluripotency and inhibit differentiation, especially during early differentiation toward neural lineage. This study suggested a new player in transcription control that governs pluripotency and differentiation.
- Embryonic stem cell
- Neural differentiation