NFIB induces functional astrocytes from human pluripotent stem cell-derived neural precursor cells mimicking in vivo astrogliogenesis

The ability to generate astrocytes from human pluripotent stem cells (hPSCs) offers a promising cellular model to study the development and physiology of human astrocytes. However, the extant methods for generating functional astrocytes required long culture periods and remained much ambiguity whether their paradigm follows the innate developmental program. In this report, we provided an efficient and rapid method for generating physiologically functional astrocytes from hPSCs. Overexpressing the nuclear factor IB (NFIB) in hPSC-derived neural precursor cells (NPCs) induced a highly enriched astrocyte population in 2 weeks. RNA sequencing and functional analyses demonstrated progressive transcriptomic and physiological changes in the cells, resembling in vivo astrocyte development. Further analyses substantiated previous results and established the MAPK pathway necessary for astrocyte differentiation. Hence, this differentiation paradigm provides a prospective in vitro model for human astrogliogenesis studies and pathophysiology of neurological diseases concerning astrocytes. RNA-seq time-course analysis of hPSC-derived neural precursor cells (NPCs) overexpressing nuclear factor IB (NFIB).