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Cited by 342T-cell and B-cell ImmunologyDevelopmental Biology and Gene RegulationGenomics and Chromatin Dynamics

Developmental gene networks: a triathlon on the course to T cell identity

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Yui, Mary A., Rothenberg, Ellen V.·2014·Nature Reviews Immunology
DOI 10.1038/nri3702PMC PMC4153685
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Abstract

Cells acquire their ultimate identities by activating combinations of transcription factors that initiate and sustain expression of the appropriate cell type-specific genes. T cell development depends on the progression of progenitor cells through three major phases, each of which is associated with distinct transcription factor ensembles that control the recruitment of these cells to the thymus, their proliferation, lineage commitment and responsiveness to T cell receptor signals, all before the allocation of cells to particular effector programmes. All three phases are essential for proper T cell development, as are the mechanisms that determine the boundaries between each phase. Cells that fail to shut off one set of regulators before the next gene network phase is activated are predisposed to leukaemic transformation.

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  • Additional factors probably collaborate with PU.1 to fine-tune the responses of Mef2c and Lmo2, because they are already declining by the end of ETP stage, multiple cell cycles before DN2b stage when PU.1 itself declines.

    “Additional factors also probably collaborate with PU.1 to fine-tune the responses of Mef2c and Lmo2, for they are already declining by the end of ETP stage, multiple cell cycles before DN2b stage when PU.1 itself declines (65, 67, 84, 121, 124) (Figure 8A).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [65]

    The ‘Transition to phase 2’ section says Spi1 (PU.1) is turned off as cells progress through DN2b, and ‘Checkpoint failure and T-cell leukemias’ says some progenitor genes terminate expression within the ETP stage. Neither passage identifies Mef2c and Lmo2 as declining by the end of ETP or says that other factors collaborate with PU.1 to fine-tune their responses. The paper describes several cell cycles before DN2b in relation to TCF-1 and GATA-3 activation, not the proposed decline of those two genes. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • The progression of cells through T-cell commitment involves the ordered downregulation of a substantial set of progenitor-specific Phase 1 transcription factors concomitant with the upregulation of T-lineage affiliated factors.

    “It has become clear that the progression of cells through T-cell commitment involves the ordered downregulation of a substantial set of progenitor-specific transcription factors, called “Phase 1” factors in this context, concomitant with the upregulation of T-lineage affiliated factors (34, 65, 84, 121, 122).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [65]

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Cited by

Sorted by citations

Authors
Yui, M. A., & Rothenberg, E. V.
Affiliations
California Institute of Technology (US)
ORCID
Venue
Nature Reviews Immunology
Publisher
Springer Science and Business Media LLC
Published
2014-07-25
Volume
14
Issue
8
Pages
529-545
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
DOI
10.1038/nri3702
PMC
PMC4153685
OpenAlex
W2035444281
Cited by
342
References
19
Citations by year
2026: 16 · 2025: 25 · 2024: 23 · 2023: 31 · 2022: 30 · 2021: 36 · 2020: 34 · 2019: 35 · 2018: 35 · 2017: 30 · 2016: 27 · 2015: 19 · 2014: 1
FWCI
2.50
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (AI064590, R56AI083514, R01AI083514, R01AI064590, R01AI095943, AI083514, AI095943)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD076915, HD076915)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
Keywords
T cell development, gene regulatory networks, transcription factors, lineage commitment, beta-selection, thymocyte differentiation, leukemic transformation, T cell receptor signaling, thymus
MeSH terms
Animals, Cell Differentiation, Cell Transformation, Neoplastic, Humans, Receptors, Antigen, T-Cell, Stem Cells, T-Lymphocytes, Thymus Gland, Transcription Factors, Signal Transduction, Leukemia, T-Cell, Cell Lineage, Mice, Receptor, Notch1, Gene Regulatory Networks

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