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METTL3-dependent m6A RNA methylation represses transposable elements derived enhancers to suppress naïve pluripotency in human pluripotent stem cells [RNA-Seq]

GSE274217 Homo sapiens Expression profiling by high throughput sequencing 28 samples 2025/04/16 GPL20301
Summary
Using a METTL3 inducible knockout (iKO) system in human expanded potential stem cells (hEPSCs), we uncovered that unlike in mESCs, METTL3 was indispensable for hPSCs’ maintenance, and that loss of METTL3 caused significant upregulation of naïve pluripotency genes accompanied with impaired hEPSCs differentiation particularly towards to both trophoblastic and amnionic lineage. Mechanistically, METTL3 iKO in hPSCs substantially increased expression of two primate-specific transposable elements (TEs), SVA_D and HERVK/LTR5_Hs.
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