Activation-Induced Cytidine Deaminase Regulates Fibroblast Growth Factor/Extracellular Signal-Regulated Kinases Signaling to Achieve the Naïve Pluripotent State During Reprogramming.

TitleActivation-Induced Cytidine Deaminase Regulates Fibroblast Growth Factor/Extracellular Signal-Regulated Kinases Signaling to Achieve the Naïve Pluripotent State During Reprogramming.
Publication TypeJournal Article
Year of Publication2019
AuthorsKumar, R, Evans, T
JournalStem Cells
Volume37
Issue8
Pagination1003-1017
Date Published2019 08
ISSN1549-4918
KeywordsAnimals, Cell Line, Cellular Reprogramming, Cellular Reprogramming Techniques, Cytidine Deaminase, Extracellular Signal-Regulated MAP Kinases, Fibroblast Growth Factors, Induced Pluripotent Stem Cells, MAP Kinase Signaling System, Mice
Abstract

Induced pluripotent stem cells (iPSCs) derived by in vitro reprogramming of somatic cells retain the capacity to self-renew and to differentiate into many cell types. Pluripotency encompasses multiple states, with naïve iPSCs considered as ground state, possessing high levels of self-renewal capacity and maximum potential without lineage restriction. We showed previously that activation-induced cytidine deaminase (AICDA) facilitates stabilization of pluripotency during reprogramming. Here, we report that Acida iPSCs, even when successfully reprogrammed, fail to achieve the naïve pluripotent state and remain primed for differentiation because of a failure to suppress fibroblast growth factor (FGF)/extracellular signal-regulated kinases (ERK) signaling. Although the mutant cells display marked genomic hypermethylation, suppression of FGF/ERK signaling by AICDA is independent of deaminase activity. Thus, our study identifies AICDA as a novel regulator of naïve pluripotency through its activity on FGF/ERK signaling. Stem Cells 2019;37:1003-1017.

DOI10.1002/stem.3023
Alternate JournalStem Cells
PubMed ID31021461
PubMed Central IDPMC6766926