Cited by 68Pluripotent Stem Cells ResearchDevelopmental Biology and Gene RegulationEpigenetics and DNA Methylation

A Dynamic Role of TBX3 in the Pluripotency Circuitry

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Russell, Ronan, Ilg, Marcus, Lin, Qiong, Wu, Guangming, Lechel, André, Bergmann, Wendy, Eiseler, Tim, Linta, Leonhard +13 more·2015·Stem Cell Reports

Abstract

Pluripotency represents a cell state comprising a fine-tuned pattern of transcription factor activity required for embryonic stem cell (ESC) self-renewal. TBX3 is the earliest expressed member of the T-box transcription factor family and is involved in maintenance and induction of pluripotency. Hence, TBX3 is believed to be a key member of the pluripotency circuitry, with loss of TBX3 coinciding with loss of pluripotency. We report a dynamic expression of TBX3 in vitro and in vivo using genetic reporter tools tracking TBX3 expression in mouse ESCs (mESCs). Low TBX3 levels are associated with reduced pluripotency, resembling the more mature epiblast. Notably, TBX3-low cells maintain the intrinsic capability to switch to a TBX3-high state and vice versa. Additionally, we show TBX3 to be dispensable for induction and maintenance of naive pluripotency as well as for germ cell development. These data highlight novel facets of TBX3 action in mESCs.

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Crossref · 10.1016/j.stemcr.2015.11.003

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  • TBX3 is critically involved in pluripotency maintenance and lineage-specific exit from the pluripotency circuitry in mouse embryonic stem cells.

    “Finally, TBX3 is not only critically involved in pluripotency maintenance but also in lineage-specific exit from the pluripotency circuitry in mouse embryonic stem cells [11–17].”

    From TBX3 is dynamically expressed in pancreatic organogenesis and fine-tunes regeneration (2023) · cites this paper as [11]

    The Results section on lineage commitment reports that removing TBX3 changes differentiation in mouse ESCs, supporting its role in lineage-specific exit. But the Discussion explicitly says TBX3 is dispensable for maintaining pluripotency, contrary to the claim that it is critically required for maintenance. No page numbers are available in our copy. (LLM, conf=0.91)

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  • Tbx3 seems expressed in a gradient in the pericentral zone.

    “Tbx3, which has been shown to act in a dosage-sensitive manner in other contexts (50), seems to be expressed in a gradient in the pericentral zone (SI Appendix, Fig. S1A).”
  • Tbx3 acts in a dosage-sensitive manner in other contexts.

    “Tbx3, which has been shown to act in a dosage-sensitive manner in other contexts (50)”
  • The Tbx3-Venus reporter system is validated.

    “To visualize the activity of the murine Tbx3 promoter at the protein level, we used a validated Tbx3-Venus (Tbx3tm1(Venus)Vmc) [11, 42–47] reporter system (Fig. 2a).”

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Authors
Russell, R., Ilg, M., Lin, Q., Wu, G., Lechel, A., Bergmann, W., Eiseler, T., Linta, L., Kumar P., P., Klingenstein, M., Adachi, K., Hohwieler, M., Sakk, O., Raab, S., Moon, A., Zenke, M., Seufferlein, T., Schöler, H. R., Illing, A., Liebau, S., & Kleger, A.
Affiliations
  • Universität Ulm (DE)
  • RWTH Aachen University (DE)
  • Max Planck Institute for Molecular Biomedicine (DE)
  • University of Tübingen (DE)
  • Geisinger Medical Center (US)
Corresponding author
Kleger, Alexander
Venue
Stem Cell Reports
Publisher
Elsevier BV
Published
2015-12
Volume
5
Issue
6
Pages
1155-1170
ISSN
2213-6711 (ISSN-L)
OpenAlex
W2191957884
Cited by
66
References
69
Citations by year
2026: 4 · 2025: 4 · 2024: 6 · 2023: 10 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 14 · 2018: 6 · 2017: 4 · 2016: 2
FWCI
1.74
Type
journal article
Language
en
Open access
Locations
  • Stem Cell Reports (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)
  • Max Planck Institute for Plasma Physics (submittedVersion)
  • RWTH Publications (RWTH Aachen) (submittedVersion, other-oa)
  • RWTH Publications (RWTH Aachen)
Funders
  • Deutsche Forschungsgemeinschaft (BO1718/4-1, K.L. 2544/1-1, ZE432/5-2)
  • Else Kröner-Fresenius-Stiftung (2011_A200)
  • Medizinischen Fakultät, Eberhard Karls Universität Tübingen
  • Baden-Württemberg Stiftung
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, pluripotency, embryonic stem cells, T-box transcription factor, naive pluripotency, epiblast, self-renewal, germ cell development, transcriptional circuitry
MeSH terms
Mouse Embryonic Stem Cells, Animals, Cells, Cultured, Gene Deletion, T-Box Domain Proteins, Cell Proliferation, Mice, Cellular Reprogramming

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