Title | Tcf15 primes pluripotent cells for differentiation. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Davies OR, Lin C-Y, Radzisheuskaya A, Zhou X, Taube J, Blin G, Waterhouse A, Smith AG, Lowell S |
Journal | Cell Rep |
Volume | 3 |
Issue | 2 |
Pagination | 472-84 |
Date Published | 2013 Feb 21 |
ISSN | 2211-1247 |
Keywords | Animals, 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. |
DOI | 10.1016/j.celrep.2013.01.017 |
Alternate Journal | Cell Rep |
PubMed ID | 23395635 |
PubMed Central ID | PMC3607254 |
Grant List | 079249 / / 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 |