Cited by 81T-cell and B-cell ImmunologyDevelopmental Biology and Gene RegulationHematopoietic Stem Cell Transplantation

Multilayered specification of the T-cell lineage fate.

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Rothenberg, Ellen V., Zhang, Jingli, Li, Long·2010·Immunological Reviews

Abstract

Summary: T‐cell development from stem cells has provided a highly accessible and detailed view of the regulatory processes that can go into the choice of a cell fate in a postembryonic, stem cell‐based system. But it has been a view from the outside. The problems in understanding the regulatory basis for this lineage choice begin with the fact that too many transcription factors are needed to provide crucial input: without any one of them, T‐cell development fails. Furthermore, almost all the factors known to provide crucial functions during the climax of T‐lineage commitment itself are also vital for earlier functions that establish the pool of multilineage precursors that would normally feed into the T‐cell specification process. When the regulatory genes that encode them are mutated, the confounding effects on earlier stages make it difficult to dissect T‐cell specification genetically. Yet both the positive and the negative regulatory events involved in the choice of a T‐cell fate are actually a mosaic of distinct functions. New evidence has emerged recently that finally provides a way to separate the major components that fit together to drive this process. Here, we review insights into T‐cell specification and commitment that emerge from a combination of molecular, cellular, and systems biology approaches. The results reveal the regulatory structure underlying this lineage decision.

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Crossref · 10.1111/j.1600-065x.2010.00964.x

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  • The transition at commitment includes general downregulation of phase 1 genes and major reorganization of active chromatin and chromatin interactions genome-wide.

    “This is part of a general downregulation of stem/progenitor associated regulatory genes (“phase 1 genes”) (34, 43) and a major reorganization of active chromatin and chromatin interactions, genome-wide, that occurs during this transition (44).”

    From Mechanisms of Action of Hematopoietic Transcription Factor PU.1 in Initiation of T-Cell Development (2019) · cites this paper as [43]

    Citation (44) is attached to the claim of genome-wide reorganization of active chromatin and chromatin interactions. Our copy discusses downregulation of stem/progenitor-associated genes in “Unleashing the expression of T-cell identity by negative regulation?” and local chromatin opening at TCR loci in “Emergence of T-cell identity,” but neither establishes the cited genome-wide reorganization. Searches for chromatin reorganization and chromatin interactions found no passage addressing it; page numbers were unavailable. (LLM, conf=0.77)

    Experimental — accuracy not yet measured
  • lck-driven Cre expression is most robust starting at the DN2 stage of development.

    “This may have occurred because expression of lck used to drive Cre expression is most robust starting at the DN2 stage of development, 2”

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Authors
Rothenberg, E. V., Zhang, J., & Li, L.
Affiliations
California Institute of Technology (US)
Corresponding author
Rothenberg, Ellen V.
Venue
Immunological Reviews
Publisher
Wiley
Published
2010-10-25
Volume
238
Issue
1
Pages
150-168
ISSN
  • 0105-2896 (ISSN-L)
  • 1600-065X
OpenAlex
W1525824369
Cited by
81
References
145
Citations by year
2025: 4 · 2024: 2 · 2023: 1 · 2021: 4 · 2020: 4 · 2019: 5 · 2017: 2 · 2016: 5 · 2015: 4 · 2014: 9 · 2013: 18 · 2012: 11
FWCI
1.04
Type
journal article
Language
en
Open access
Locations
  • Immunological Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders
  • National Heart, Lung, and Blood Institute (R33HL089123)
  • National Cancer Institute (R01CA90233, R01CA090233, RC2CA148278)
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
  • Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
Keywords
T cell development, lineage commitment, transcription factors, hematopoietic stem cells, transcriptional regulation, systems biology
MeSH terms
Animals, Cell Differentiation, Hematopoietic Stem Cells, Humans, Repressor Proteins, T-Lymphocytes, T-Lymphocyte Subsets, Gene Expression Regulation, Developmental, Cell Lineage, Tumor Suppressor Proteins, Gene Regulatory Networks

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