RNA m6A modification regulates cell fate transition between pluripotent stem cells and 2‐cell‐like cells

Abstract

AbstractN6‐methyladenosine (m6A) exerts essential roles in early embryos, especially in the maternal‐to‐zygotic transition stage. However, the landscape and roles of RNA m6A modification during the transition between pluripotent stem cells and 2‐cell‐like (2C‐like) cells remain elusive. Here, we utilised ultralow‐input RNA m6A immunoprecipitation to depict the dynamic picture of transcriptome‐wide m6A modifications during 2C‐like transitions. We found that RNA m6A modification was preferentially enriched in zygotic genome activation (ZGA) transcripts and MERVL with high expression levels in 2C‐like cells. During the exit of the 2C‐like state, m6A facilitated the silencing of ZGA genes and MERVL. Notably, inhibition of m6A methyltransferase METTL3 and m6A reader protein IGF2BP2 is capable of significantly delaying 2C‐like state exit and expanding 2C‐like cells population. Together, our study reveals the critical roles of RNA m6A modification in the transition between 2C‐like and pluripotent states, facilitating the study of totipotency and cell fate decision in the future.