Rapid and Efficient Induction of Functional Astrocytes from Human Pluripotent Stem Cells

Current protocols for differentiation of human pluripotent stem cells to astrocytes are slow and ine cient, and characterization of the generated cells is incomplete.These shortcomings severely limit research on the biology of human astrocytes and their involvement in neurological disorders.Here we capitalized on recent transcription factor-driven methods to develop a novel protocol for astrocyte differentiation.We demonstrate that overexpression of two gliogenic transcription factors, Sox9 and N b, in human pluripotent stem cells rapidly and e ciently gives rise to a highly homogenous population of astrocytes as early as 7 days post-transduction.After 14 days, these induced astrocytes \(iAs) exhibit molecular signatures and functional properties closely resembling those of adult human astrocytes.The iAs also recapitulate disease phenotype in a genome-engineered model of Alexander disease.Our approach provides an easy, time-e cient, effective and scalable method that will provide new opportunities for studies on the role of human astrocytes in health and disease.