Transcriptomic analysis of the m6A reader <i>YTHDF2</i> in the maintenance and differentiation of human embryonic stem cells

As the most abundant internal modification on mRNAs, N6-methyladenosine (m6A) has been discovered to be involved in different biological processes. Mostly determined by m6A methyl-transferases (m6A writers) and demethylases (m6A erasers), different cell types possess differential m6A profiles of transcriptomes. However, the interpretation of the m6A-encoded epitranscriptomic information needs m6A readers to bind and recruit different machinery for regulating the target mRNAs, which in turn, may regulate cell fates. The functions of the m6A readers in the regulation of the maintenance and differentiation of human embryonic stem cells (hESCs) remain largely unknown. In this study, we deleted the whole genomic region of the m6A reader YTHDF2 and discovered that YTHDF2 is dispensable for the maintenance, but important for the differentiation of hESCs, especially for the differentiation towards ectoderm. Furthermore, we identified the m6A-modified ROBO1 mRNAs as potential targets by YTHDF2 in regulating hESC to neuroectoderm differentiation. This study reveals the potential roles of the m6A reader YTHDF2 in regulating the specification of neuroectodermal cell fate.