NAT10-mediated ac4 C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA

  • Cell Prolif. 2023 Dec 2:e13577. doi: 10.1111/cpr.13577.
Junbang Ge  1 ,  Zhaoxia Wang  2 ,  Ji Wu  1  3  4
Affiliations
  • 1. Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China.
  • 2. Laboratory Animal Center of Instrumental Analysis Center, Shanghai Jiao Tong University, Shanghai, China.
  • 3. Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, China.
  • 4. Shanghai Key Laboratory of Reproductive Medicine, Shanghai, China.
PMID: 38041497 DOI: 10.1111/cpr.13577
Abstract

Cell fate determination in mammalian development is complex and precisely controlled and accumulating evidence indicates that epigenetic mechanisms are crucially involved. N4 -acetylcytidine (ac4 C) is a recently identified modification of messenger RNA (mRNA); however, its functions are still elusive in mammalian. Here, we show that N-acetyltransferase 10 (NAT10)-mediated ac4 C modification promotes ectoderm differentiation of human embryonic stem cells (hESCs) by acetylating nuclear receptor subfamily 2 group F member 1 (NR2F1) mRNA to enhance translation efficiency (TE). Acetylated RNA immunoprecipitation Sequencing (acRIP-seq) revealed that levels of ac4 C modification were higher in ectodermal neuroepithelial progenitor (NEP) cells than in hESCs or mesoendoderm cells. In addition, integrated analysis of acRIP-seq and ribosome profiling Sequencing revealed that NAT10 catalysed ac4 C modification to improve TE in NEP cells. RIP-qRT-PCR analysis identified an interaction between NAT10 and NR2F1 mRNA in NEP cells and NR2F1 accelerated the nucleus-to-cytoplasm translocation of yes-associated protein 1, which contributed to ectodermal differentiation of hESCs. Collectively, these findings point out the novel regulatory role of ac4 C modification in the early ectodermal differentiation of hESCs and will provide a new strategy for the treatment of neuroectodermal defects diseases.

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