Developmental DNA demethylation is a determinant of neural stem cell identity and gliogenic competence.

ABSTRACT: DNA methylation is extensively reconfigured during development, but the functional significance and cell type-specific dependencies of DNA demethylation in lineage specification remain poorly understood. Here, we demonstrate that developmental DNA demethylation, driven by ten-eleven translocation 1/2/3 (TET1/2/3) enzymes, is essential for establishment of neural stem cell (NSC) identity and gliogenic potential. We find that loss of all three TETs during NSC specification is dispensable for neural induction and neuronal differentiation but critical for astrocyte and oligodendrocyte formation, demonstrating a selective loss of glial competence. Mechanistically, TET-mediated demethylation was essential for commissioning neural-specific enhancers in proximity to master neurodevelopmental and g

SUBMITTER: MacArthur IC 

PROVIDER: S-EPMC11352921 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature