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Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm

Waghray, Avinash; Saiz, Néstor; Jayaprakash, Anitha D.; Freire, Ana G.; Papatsenko, Dmitri; Pereira, Carlos Filipe LU ; Lee, Dung Fang; Brosh, Ran; Chang, Betty and Darr, Henia, et al. (2015) In Stem Cell Reports 5(1). p.97-110
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... (More)

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.

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published
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Stem Cell Reports
volume
5
issue
1
pages
14 pages
publisher
Cell Press
external identifiers
  • scopus:84937523983
ISSN
2213-6711
DOI
10.1016/j.stemcr.2015.05.009
language
English
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no
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761095d7-39bc-4eba-b099-33566a933075
date added to LUP
2017-10-02 17:26:08
date last changed
2017-10-12 09:34:00
@article{761095d7-39bc-4eba-b099-33566a933075,
  abstract     = {<p>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.</p>},
  author       = {Waghray, Avinash and Saiz, Néstor and Jayaprakash, Anitha D. and Freire, Ana G. and Papatsenko, Dmitri and Pereira, Carlos Filipe and Lee, Dung Fang and Brosh, Ran and Chang, Betty and Darr, Henia and Gingold, Julian and Kelley, Kevin and Schaniel, Christoph and Hadjantonakis, Anna Katerina and Lemischka, Ihor R.},
  issn         = {2213-6711},
  language     = {eng},
  month        = {07},
  number       = {1},
  pages        = {97--110},
  publisher    = {Cell Press},
  series       = {Stem Cell Reports},
  title        = {Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2015.05.009},
  volume       = {5},
  year         = {2015},
}