title: Tcf15 primes pluripotent cells for differentiation.
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.
authors: Institute for Stem Cell Research, MRC Centre for Regenerative Medicine, The University of Edinburgh, Edinburgh EH16 4UU, UK.
authors: Owen R
authors: OR
authors: Davies
authors: Chia-Yi
authors: CY
authors: Lin
authors: Aliaksandra
authors: A
authors: Radzisheuskaya
authors: Xinzhi
authors: X
authors: Zhou
authors: Jessica
authors: J
authors: Taube
authors: Guillaume
authors: G
authors: Blin
authors: Anna
authors: A
authors: Waterhouse
authors: Andrew J H
authors: AJ
authors: Smith
authors: Sally
authors: S
authors: Lowell
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002478:Cells, Cultured; D015536:Down-Regulation; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D004707:Endoderm / Q000166:cytology / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000378:metabolism; D051379:Mice; D000071317:Nanog Homeobox Protein; D051857:Otx Transcription Factors / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D005346:Fibroblast Growth Factors; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; D051857:Otx Transcription Factors; C475540:Nanog protein, mouse; C497660:Otx2 protein, mouse; C093234:Tcf15 protein, mouse
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