Authors: | Waghray, A.; Saiz, N.; Jayaprakash, A. D.; Freire, A. G.; Papatsenko, D.; Pereira, C. F.; Lee, D. F.; Brosh, R.; Chang, B.; Darr, H.; Gingold, J.; Kelley, K.; Schaniel, C.; Hadjantonakis, A. K.; Lemischka, I. R. |
Article Title: | Tbx3 controls Dppa3 levels and exit from pluripotency toward mesoderm |
Abstract: | Tbx3, a member of the T-box family, plays important roles in development, stem cells, nuclear reprogramming, and cancer. Loss of Tbx3 induces differentiation in mouse embryonic stem cells (mESCs). However, we show that mESCs exist in an alternate stable pluripotent state in the absence of Tbx3. In-depth transcriptome analysis of this mESC state reveals Dppa3 as a direct downstream target of Tbx3. Also, Tbx3 facilitates the cell fate transition from pluripotent cells to mesoderm progenitors by directly repressing Wnt pathway members required for differentiation. Wnt signaling regulates differentiation of mESCs into mesoderm progenitors and helps to maintain a naive pluripotent state. We show that Tbx3, a downstream target of Wnt signaling, fine tunes these divergent roles of Wnt signaling in mESCs. In conclusion, we identify a signaling-TF axis that controls the exit of mESCs from a self-renewing pluripotent state toward mesoderm differentiation. © 2015 The Authors. |
Keywords: | controlled study; protein expression; unclassified drug; nonhuman; animal cell; mouse; gene expression; embryonic stem cell; cell fate; cell renewal; cell differentiation; transcriptomics; pluripotent stem cell; cell marker; wnt protein; mesoderm; t box transcription factor; wnt signaling pathway; priority journal; article; dppa3 protein; transcription factor tbx3 |
Journal Title: | Stem Cell Reports |
Volume: | 5 |
Issue: | 1 |
ISSN: | 2213-6711 |
Publisher: | Cell Press |
Date Published: | 2015-07-14 |
Start Page: | 97 |
End Page: | 110 |
Language: | English |
DOI: | 10.1016/j.stemcr.2015.05.009 |
PROVIDER: | scopus |
PUBMED: | 26095607 |
PMCID: | PMC4618439 |
DOI/URL: | |
Notes: | Export Date: 2 September 2015 -- Source: Scopus |