Fig. 8: METTL3 functions in human placenta development.

During normal placentation in vivo, CTBs exhibit elevated METTL3 expression (+++) and moderate level of H3K27ac (+), facilitating appropriate trophoblast proliferation and differentiation. In placentas affected by PE, CTBs display a reduction in METTL3 expression (+) concomitant with a marked increase in H3K27ac expression (+++). In vitro, hTSCs express METTL3, which catalyzes m⁶A modification on target transcripts such as EP300, JUND, and EZH2, ensuring their proper turnover. These transcripts are crucial for H3K27ac and H3K27me3 depositions, maintaining hTSCs identity and safeguarding their differentiation potential. Conversely, loss of METTL3 in hTSCs disrupts epigenomic homeostasis, potentially leading to premature senescence, activation of inflammatory pathways, and the emergence of an in vivo PE-like signature.