Rapid induction of gliogenesis inOLIG2andNKX2.2-expressing progenitors-derived spheroids

Abstract

Glial cells are crucial for the developing central nervous system and the maintenance of chemical homeostasis. The process of gliogenesis has been well studied in the rodent brain but it remains unknown in human brain. In addition, rodent glial cells differ from human counterparts in terms of morphologies, functions, and anatomical locations. Cerebral organoids (also referred to as spheroids) derived from human pluripotent stem cells (hPSCs) have been developed and as suitable cell-based models for researching developmental and neurodegenerative diseases. The in vitro generation of glia, including astrocytes and oligodendrocytes, from such organoids represents a promising tool to model neuronal diseases. Here, we showed that three-dimensional (3D) culture of OLIG2 and NKX2.2- expressing neurospheres produced efficiently mature astrocytes and oligodendrocytes in terms of morphologies and expression pattern recapitulating native 3D environment. Our findings provide important insights for developmental research of the human brain and glial specification that may facilitate patient-specific disease modeling.