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Tcf15 primes pluripotent cells for differentiation.

TitleTcf15 primes pluripotent cells for differentiation.
Publication TypeJournal Article
Year of Publication2013
AuthorsDavies OR, Lin C-Y, Radzisheuskaya A, Zhou X, Taube J, Blin G, Waterhouse A, Smith AG, Lowell S
JournalCell Rep
Volume3
Issue2
Pagination472-84
Date Published2013 Feb 21
ISSN2211-1247
KeywordsAnimals, Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation, Cells, Cultured, Down-Regulation, Embryo, Mammalian, Embryonic Stem Cells, Endoderm, Fibroblast Growth Factors, Gene Expression Regulation, Developmental, Homeodomain Proteins, Mice, Otx Transcription Factors, Signal Transduction
Abstract

The events that prime pluripotent cells for differentiation are not well understood. Inhibitor of DNA binding/differentiation (Id) proteins, which are inhibitors of basic helix-loop-helix (bHLH) transcription factor activity, contribute to pluripotency by blocking sequential transitions toward differentiation. Using yeast-two-hybrid screens, we have identified Id-regulated transcription factors that are expressed in embryonic stem cells (ESCs). One of these, Tcf15, is also expressed in the embryonic day 4.5 embryo and is specifically associated with a novel subpopulation of primed ESCs. An Id-resistant form of Tcf15 rapidly downregulates Nanog and accelerates somatic lineage commitment. We propose that because Tcf15 can be held in an inactive state through Id activity, it may prime pluripotent cells for entry to somatic lineages upon downregulation of Id. We also find that Tcf15 expression is dependent on fibroblast growth factor (FGF) signaling, providing an explanation for how FGF can prime for differentiation without driving cells out of the pluripotent state.

DOI10.1016/j.celrep.2013.01.017
Alternate JournalCell Rep
PubMed ID23395635
PubMed Central IDPMC3607254
Grant List079249 / / Wellcome Trust / United Kingdom
BB/I006680/1 / / Biotechnology and Biological Sciences Research Council / United Kingdom
G15381 / / Biotechnology and Biological Sciences Research Council / United Kingdom
WT082232AIA / / Wellcome Trust / United Kingdom