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METTL3-dependent m6A modification programs human neural progenitor cell proliferation

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

ORGANISM(S): Homo sapiens

PROVIDER: GSE242522 | GEO | 2023/11/22

REPOSITORIES: GEO

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METTL3-Dependent N6-Methyladenosine Modification Programs Human Neural Progenitor Cell Proliferation.

Project description:METTL3, a methyltransferase responsible for N6-methyladenosine (m6A) modification, plays key regulatory roles in mammal central neural system (CNS) development. However, the specific epigenetic mechanisms governing human CNS development remain poorly elucidated. Here, we generated small-molecule-assisted shut-off (SMASh)-tagged hESC lines to reduce METTL3 protein levels, and found that METTL3 is not required for human neural progenitor cell (hNPC) formation and neuron differentiation. However, METTL3 deficiency inhibited hNPC proliferation by reducing SLIT2 expression. Mechanistic studies revealed that METTL3 degradation in hNPCs significantly decreased the enrichment of m6A in SLIT2 mRNA, consequently reducing its expression. Our findings reveal a novel functional target (SLIT2) for METTL3 in hNPCs and contribute to a better understanding of m6A-dependent mechanisms in hNPC proliferation.

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METTL3-dependent m6A modification programs human neural progenitor cell proliferation [RNA-seq]

Project description:To investigate whether the role of METTL3 in hNPCs is dependent on its m6A activity,samples form neural progenitor cell (NPC) differentiation in the small molecule-assisted shut-off (SMASh) tagged hESC groups were collected. Gene expression levels were quantitated by RNA-seq analysis, and the potential target genes were identified by MeRIP-seq analysis and RIP-seq.

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