<b>Supporting Data for </b><b><i>"METTL3-dependent Centromeric RNA-m6A </i></b>

Across hEPSCs, hESCs, hTSCs, blastoids, and donated embryos, METTL3 perturbation impaired stem-cell fitness, pluripotency exit, trophoblast competence and developmental progression. In hTSCs, METTL3 supported cytotrophoblast-like identity through epigenetic regulation involving EP300, JUND and EZH2.

Mitotic abnormalities, chromosome missegregation and altered DNA content were particularly prominent in early stem-cell states. METTL3 loss also disrupted CENPA maintenance and centromeric alpha-satellite RNA regulation, including ALR m6A, chromatin state, and CENPA/YTHDC1-associated enrichment. These findings identify a developmental-stage-associated METTL3 dependency with implications for genome-quality control and developmental safety.</p>