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Cited by 285Pluripotent Stem Cells ResearchAnimal Genetics and ReproductionDevelopmental Biology and Gene Regulation

Tbx3 improves the germ-line competency of induced pluripotent stem cells

Open access
Han, Jianyong, Yuan, Ping, Yang, Henry, Zhang, Jinqiu, Soh, Boon Seng, Li, Pin, Lim, Siew Lan, Cao, Suying +6 more·2010·Nature
DOI 10.1038/nature08735PMC PMC2901797
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Abstract

Induced pluripotent stem (iPS) cells can be obtained by the introduction of defined factors into somatic cells. The combination of Oct4 (also known as Pou5f1), Sox2 and Klf4 (which we term OSK) constitutes the minimal requirement for generating iPS cells from mouse embryonic fibroblasts. These cells are thought to resemble embryonic stem cells (ESCs) on the basis of global gene expression analyses; however, few studies have tested the ability and efficiency of iPS cells to contribute to chimaerism, colonization of germ tissues, and most importantly, germ-line transmission and live birth from iPS cells produced by tetraploid complementation. Using genomic analyses of ESC genes that have roles in pluripotency and fusion-mediated somatic cell reprogramming, here we show that the transcription factor Tbx3 significantly improves the quality of iPS cells. iPS cells generated with OSK and Tbx3 (OSKT) are superior in both germ-cell contribution to the gonads and germ-line transmission frequency. However, global gene expression profiling could not distinguish between OSK and OSKT iPS cells. Genome-wide chromatin immunoprecipitation sequencing analysis of Tbx3-binding sites in ESCs suggests that Tbx3 regulates pluripotency-associated and reprogramming factors, in addition to sharing many common downstream regulatory targets with Oct4, Sox2, Nanog and Smad1. This study underscores the intrinsic qualitative differences between iPS cells generated by different methods, and highlights the need to rigorously characterize iPS cells beyond in vitro studies.

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Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • TBX3 acts as a transcription activator to upregulate target gene expression.

    “TBX3 acts as a transcription activator to upregulate target gene expression.”

    From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [62]

    The paper reports that Tbx3 binds regulatory targets in embryonic stem cells and that some pluripotency-associated genes are expressed at higher levels in OSKT than OSK iPS cells (full-text section labeled Abstract; no page supplied). It does not establish that Tbx3 directly acts as a transcriptional activator of those targets; it says the precise mechanism needs clarification. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Tbx3 is involved in the carcinogenesis of multiple types of human cancers.

    “As Tbx3 is involved in the carcinogenesis of multiple types of human cancers, our findings suggest an important target for anti-cancer drug development.”

    From Novel HDAC5-interacting motifs of Tbx3 are essential for the suppression of E-cadherin expression and for the promotion of metastasis in hepatocellular carcinoma (2018) · cites this paper as [26]

    The Abstract discusses Tbx3 in mouse stem-cell pluripotency and reprogramming, not its role in human carcinogenesis. Searches for carcinogenesis and human cancers found no passage in our copy addressing the claim. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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References 25 · Cited by 285

Research works printed but not linked: 24

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Authors
Han, J., Yuan, P., Yang, H., Zhang, J., Soh, B. S., Li, P., Lim, S. L., Cao, S., Tay, J., Orlov, Y. L., Lufkin, T., Ng, H.-H., Tam, W.-L., & Lim, B.
Affiliations
  • Genome Institute of Singapore (SG)
  • Singapore Immunology Network (SG)
  • National University of Singapore (SG)
  • Beth Israel Deaconess Medical Center (US)
Corresponding author
  • Tam, Wai-Leong
  • Lim, Bing
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2010-02
Volume
463
Issue
7284
Pages
1096-1100
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/nature08735
PMC
PMC2901797
OpenAlex
W1971271231
Cited by
285
References
25
Citations by year
2026: 5 · 2025: 9 · 2024: 4 · 2023: 10 · 2022: 8 · 2021: 10 · 2020: 12 · 2019: 13 · 2018: 9 · 2017: 10 · 2016: 18 · 2015: 24 · 2014: 28 · 2013: 32 · 2012: 37
FWCI
16.17
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • National University of Singapore (submittedVersion)
  • RePEc: Research Papers in Economics (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (AI-54973, R01AI054973)
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK047636, R01DK047636)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
Keywords
TBX3, induced pluripotent stem cells, germline transmission, chimerism, somatic cell reprogramming, Oct4, SOX2, KLF4, transcription factor binding sites, pluripotency, germ cells, tetraploid complementation
MeSH terms
Nanog Homeobox Protein, Kruppel-Like Factor 4, Animals, Cell Fusion, Chimera, Embryo, Mammalian, Female, Fibroblasts, Gene Expression Regulation, Germ Cells, Gonads, Male, Mice, Transgenic, Regulatory Sequences, Nucleic Acid, Transcription, Genetic, Transduction, Genetic, Homeodomain Proteins, T-Box Domain Proteins, Gene Expression Profiling, Chromatin Immunoprecipitation, Octamer Transcription Factor-3, Mice, Kruppel-Like Transcription Factors, Smad1 Protein, SOXB1 Transcription Factors, Induced Pluripotent Stem Cells, Cellular Reprogramming

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