Open AccessN6-methyladenosine (m 6 A) depletion regulates pluripotency exit by activating signaling pathways in embryonic stem cells
Author(s) -
Kang-Xuan Jin,
Ru-Juan Zuo,
Konstantinos Anastassiadis,
Arne Klungland,
Carsten Marr,
Adam Filipczyk
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2105192118
Subject(s) - homeobox protein nanog , rex1 , embryonic stem cell , microbiology and biotechnology , stem cell , nanog homeobox protein , cell fate determination , cellular differentiation , transcription factor , biology , induced pluripotent stem cell , chemistry , genetics , gene
Significance Dynamic deposition of the N6-methyladenosine (m6 A) modification on messenger RNA (mRNA) regulates pluripotency in embryonic stem cells. Reports show that depletion of m6 A 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. m6 A depletion activates key signaling pathways involved in pluripotency versus commitment decisions. This occurs independently of m6 A control over TF mRNA transcript stability. m6 A deposition regulates TF protein expression levels by activating pErk and pAkt signaling to enact cell-fate determination in pluripotent stem cells.