NFIA is a gliogenic switch enabling rapid derivation of functional human astrocytes from pluripotent stem cells.
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ABSTRACT: The mechanistic basis of gliogenesis, which occurs late in human development, is poorly understood. Here we identify nuclear factor IA (NFIA) as a molecular switch inducing human glial competency. Transient expression of NFIA is sufficient to trigger glial competency of human pluripotent stem cell-derived neural stem cells within 5 days and to convert these cells into astrocytes in the presence of glial-promoting factors, as compared to 3-6 months using current protocols. NFIA-induced astrocytes promote synaptogenesis, exhibit neuroprotective properties, display calcium transients in response to appropriate stimuli and engraft in the adult mouse brain. Differentiation involves rapid but reversible chromatin remodeling, glial fibrillary acidic protein (GFAP) promoter demethylation and a str
SUBMITTER: Tchieu J
PROVIDER: S-EPMC6591152 | biostudies-literature | 2019 Mar
REPOSITORIES: biostudies-literature
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