Context-dependent wiring of Sox2 regulatory networks for self-renewal of embryonic and trophoblast stem cells

Sox2 is a transcription factor required for the maintenance of pluripotency. It also plays an essential role in different types of multipotent stem cells, raising the possibility that Sox2 governs the common stemness phenotype. Here we show that Sox2 is a critical downstream target of fibroblast gro...

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Bibliographic Details
Published in:Molecular cell 2013-11, Vol.52 (3), p.380-392
Main Authors: Adachi, Kenjiro, Nikaido, Itoshi, Ohta, Hiroshi, Ohtsuka, Satoshi, Ura, Hiroki, Kadota, Mitsutaka, Wakayama, Teruhiko, Ueda, Hiroki R, Niwa, Hitoshi
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation - genetics
Cell Line
Embryonic Development - genetics
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Fibroblast Growth Factors - metabolism
Gene Expression Regulation, Developmental
Mice
Pluripotent Stem Cells - cytology
Pluripotent Stem Cells - metabolism
Signal Transduction - genetics
SOXB1 Transcription Factors - immunology
SOXB1 Transcription Factors - metabolism
Stem Cells - cytology
Stem Cells - metabolism
Transcription Factor AP-2 - metabolism
Trophoblasts - cytology
Trophoblasts - metabolism
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Summary:Sox2 is a transcription factor required for the maintenance of pluripotency. It also plays an essential role in different types of multipotent stem cells, raising the possibility that Sox2 governs the common stemness phenotype. Here we show that Sox2 is a critical downstream target of fibroblast growth factor (FGF) signaling, which mediates self-renewal of trophoblast stem cells (TSCs). Sustained expression of Sox2 together with Esrrb or Tfap2c can replace FGF dependency. By comparing genome-wide binding sites of Sox2 in embryonic stem cells (ESCs) and TSCs combined with inducible knockout systems, we found that, despite the common role in safeguarding the stem cell state, Sox2 regulates distinct sets of genes with unique functions in these two different yet developmentally related types of stem cells. Our findings provide insights into the functional versatility of transcription factors during embryogenesis, during which they can be recursively utilized in a variable manner within discrete network structures.
ISSN:1097-2765
1097-4164
DOI:10.1016/j.molcel.2013.09.002