2. Academic Validation
  3. Transcriptomic analysis of the m6A reader YTHDF2 in the maintenance and differentiation of human embryonic stem cells

Transcriptomic analysis of the m6A reader YTHDF2 in the maintenance and differentiation of human embryonic stem cells

  • Stem Cells. 2025 Jun 24;43(7):sxaf032. doi: 10.1093/stmcls/sxaf032.
Boshi Feng 1,  Yanxi Chen 1,  Huanchang Tu 1,  Jin Zhang 1,  Lingling Tong 1,  Xiaohan Lyu 2,  Aaron Trent Irving 2 3,  Di Chen 1 3 4
Affiliations

Affiliations

  • 1 Center for Reproductive Medicine of The Second Affiliated Hospital, Center for Regeneration and Cell Therapy of Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310003, China.
  • 2 Centre of Infection Immunity and Cancer (IIC) of Zhejiang University-University of Edinburgh Institute (ZJU-UoE Institute), Zhejiang University School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310029, China.
  • 3 Edinburgh Medical School: Biomedical Sciences, College of Medicine and Veterinary Medicine, The University of Edinburgh, Edinburgh EH8 9AG, United Kingdom.
  • 4 State Key Laboratory of Biobased Transportation Fuel Technology, Haining, Zhejiang 314400, China.
PMID: 40418739 DOI: 10.1093/stmcls/sxaf032
Abstract

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.

Keywords

ROBO1; YTHDF2; hESCs; neural development.

Figures
Products