GSE133207
JMJD3 and UTX Determine Fidelity and Lineage Specification of Human Neural Progenitor Cells [ATAC-seq]
Neurogenesis entails a highly orchestrated process from pluripotent to neural cell fates including progenitors (NPCs) and various neural subtypes. However, the precise epigenetic mechanisms underlying the fate decision remain poorly understood. Here, we deleted KDM6s (JMJD3 or/and UTX), the demethylases for H3K27me3, in human embryonic stem cells (hESCs) and show that their deletion does not impede NPC generation from hESCs. However, KDM6-deficient NPCs exhibit poor proliferation and fail to become neurons and glia. Mechanistically, KDM6 deficiency leads to H3K27me3 accumulation and blockade of DNA accessibility at loci essential for neurogenesis, thus hinder the fate transition from NPCs to neural subtypes. Our findings uncover an essential role of KDM6s in neurogenesis and highlight the contribution of individual epigenetic regulators in specifying lineage fidelity and fate decision during human development. Overall design: We compared the chromatin accessibility of  NPCs by ATAC-seq.