GSE104232 NFIA enables the rapid derivation of functional, human astrocytes from pluripotent stem cells by modulating G1 cell cycle length

Contributors : Lorenz Studer ; Jason TchieuSeries Type : Expression profiling by high throughput sequencing ; Genome binding/occupancy profiling by high throughput sequencingOrganism : Homo sapiensThe development of the central nervous system (CNS) depends on the orchestrated generation of neurons and glia from neural stem cells (NSCs). Although NSCs generate both cell types, they are produced sequentially as neurons are born first and glia later. In humans, this timing is extremely protracted and the underlying mechanisms remain unknown. Deriving glial cells such as astrocytes from human pluripotent stem cells requires 3-6 months of differentiation, greatly impeding their use in human disease modeling and regenerative medicine. Here, we report that expression of the transcription factor nuclear factor IA (NFIA) is sufficient to trigger glial competency in highly neurogenic NSCs and enables the derivation of human astrocytes within 10-12 days. NFIA-induced astrocytes are functional and shown to promote synaptogenesis, protect neurons and generate calcium transients. The mechanism of NFIA-induced glial competency involves rapid but reversible chromatin remodeling, demethylation of the GFAP promoter and a striking effect on the cell cycle. NFIA titration and pharmacological studies indicate that acquisition of a glial-compatible G1 length is critical for achieving glial competency. Our results offer mechanistic insights into human glial competency and enable the routine use ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Genome binding/occupancy profiling by high throughput sequencing Homo sapiens Source Type: research