期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2021
卷号：118
期号：51
DOI：10.1073/pnas.2105192118
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Significance
Dynamic deposition of the N6-methyladenosine (m
6A) modification on messenger RNA (mRNA) regulates pluripotency in embryonic stem cells. Reports show that depletion of m
6A abundances increases the mRNA stability of pluripotency and lineage transcription factors (TFs) alike. If the mRNAs of these two TF groups become stabilized, it remains unclear how the pluripotency or lineage commitment decision is implemented. Quantification of pluripotency TFs live at single-cell resolution over generations shows long-term preservation of both pluripotency and priming. m
6A depletion activates key signaling pathways involved in pluripotency versus commitment decisions. This occurs independently of m
6A control over TF mRNA transcript stability. m
6A deposition regulates TF protein expression levels by activating pErk and pAkt signaling to enact cell-fate determination in pluripotent stem cells.
N6-methyladenosine (m
6A) deposition on messenger RNA (mRNA) controls embryonic stem cell (ESC) fate by regulating the mRNA stabilities of pluripotency and lineage transcription factors (TFs) [P. J. Batista et al.,
Cell Stem Cell 15, 707–719 (2014); Y. Wang et al.,
Nat. Cell Biol. 16, 191–198 (2014); and S. Geula et al.,
Science 347, 1002–1006 (2015)
