METTL3 and METTL14 determine human neural fate specifications.

ABSTRACT: METTL3/METTL14, the canonical methyltransferase complex modifying N6-methyladenosine (m6A) on mRNAs, plays critical roles in development and various diseases. However, its precise functions in specifying neural fate from human embryonic stem cells (hESCs) remain poorly understood. Here, we demonstrate, using an inducible knockout system, that METTL3/METTL14 deletion impairs the generation of neural progenitor cells (NPCs) from hESCs. Furthermore, inducible METTL3/METTL14-deficient NPCs exhibit compromised long-term proliferation and fail to differentiate into neurons. Mechanistically, METTL3 is enriched in gene loci essential for neurogenesis and chromatin remodeling in human NPCs, thereby promoting chromatin accessibility at these sites. Importantly, forced expression of BRM, a catalytic

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12700100 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature