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JMJD3 and UTX Determine Fidelity and Lineage Specification of Human Neural Progenitor Cells

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE118999 | GEO | 2019/12/02

REPOSITORIES: GEO

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JMJD3 and UTX determine fidelity and lineage specification of human neural progenitor cells.

Project description:Neurogenesis, a highly orchestrated process, entails the transition from a pluripotent to neural state and involves neural progenitor cells (NPCs) and neuronal/glial subtypes. However, the precise epigenetic mechanisms underlying fate decision remain poorly understood. Here, we delete KDM6s (JMJD3 and/or UTX), the H3K27me3 demethylases, 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 a failure to differentiate into neurons and glia. Mechanistically, both JMJD3 and UTX are found to be enriched in gene loci essential for neural development in hNPCs, and KDM6 impairment leads to H3K27me3 accumulation and blockade of DNA accessibility at these genes. Interestingly, forced expression of neuron-specific chromatin remodelling BAF (nBAF) rescues the neuron/glia defect in KDM6-deficient NPCs despite H3K27me3 accumulation. Our findings uncover the differential requirement of KDM6s in specifying NPCs and neurons/glia and highlight the contribution of individual epigenetic regulators in fate decisions in a human development model.

| S-EPMC6971254 | biostudies-literature

JMJD3 and UTX Determine Fidelity and Lineage Specification of Human Neural Progenitor Cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2019-12-02 | GSE133209 | GEO

JMJD3 and UTX Determine Fidelity and Lineage Specification of Human Neural Progenitor Cells [UTX ChIP]

Project description: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.

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JMJD3 and UTX Determine Fidelity and Lineage Specification of Human Neural Progenitor Cells [ChIP-Seq]

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JMJD3 and UTX Determine Fidelity and Lineage Specification of Human Neural Progenitor Cells [ATAC-seq]

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