Tcf15 Primes Pluripotent Cells for Differentiation

Owen R. Davies, Chia-Yi Lin, Aliaksandra Radzisheuskaya, Xinzhi Zhou, Jessica Taube, Guillaume Blin, Anna Waterhouse, Andrew Smith, Sally Lowell

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.
Original languageEnglish
Pages (from-to)472-484
JournalCell Reports
Volume3
Issue number2
Early online date7 Feb 2013
DOIs
Publication statusPublished - Feb 2013

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