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Cited by 50Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationEpigenetics and DNA Methylation

Tbx3 Controls Dppa3 Levels and Exit from Pluripotency toward Mesoderm

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Waghray, Avinash, Saiz, Néstor, Jayaprakash, Anitha D., Freire, Ana G., Papatsenko, Dmitri, Pereira, Carlos-Filipe, Lee, Dung-Fang, Brosh, Ran +7 more·2015·Stem Cell Reports
DOI 10.1016/j.stemcr.2015.05.009PMC PMC4618439
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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.

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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.
Affiliations
  • Icahn School of Medicine at Mount Sinai (US)
  • Memorial Sloan Kettering Cancer Center (US)
  • Universidade do Porto (PT)
Corresponding author
Lemischka, Ihor R.
ORCID
Venue
Stem Cell Reports
Publisher
Elsevier BV
Published
2015-07
Volume
5
Issue
1
Pages
97-110
ISSN
2213-6711 (ISSN-L)
DOI
10.1016/j.stemcr.2015.05.009
PMC
PMC4618439
OpenAlex
W1669125802
Cited by
50
References
77
Citations by year
2026: 5 · 2024: 3 · 2023: 2 · 2022: 1 · 2021: 5 · 2020: 6 · 2019: 9 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 2
FWCI
2.75
Type
journal article
Language
en
Open access
Licence
Locations
  • Stem Cell Reports (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Lund University Publications (Lund University) (submittedVersion)
Funders
  • National Institutes of Health
  • Fundação para a Ciência e a Tecnologia
  • National Institute of General Medical Sciences (R01GM078465)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (T32HD075735)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
Keywords
TBX3, DPPA3, mouse embryonic stem cells, naive pluripotency, mesoderm differentiation, Wnt signaling, self-renewal, transcriptome
MeSH terms
Mouse Embryonic Stem Cells, Animals, Cell Differentiation, Chromosomal Proteins, Non-Histone, Mesoderm, Repressor Proteins, Gene Expression Regulation, Developmental, Cell Lineage, T-Box Domain Proteins, Pluripotent Stem Cells, Mice, Wnt Signaling Pathway

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