Evidence map›Paper›PMID 25846797›Full record

ArticleGenes & development2015

Regulation of early T-lineage gene expression and developmental progression by the progenitor cell transcription factor PU.1.

Ameya Champhekar, Sagar S Damle, George Freedman, Sebastian Carotta, Stephen L Nutt, Ellen V Rothenberg

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 72 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Review
  6. Case Report: A novelFrontiers in immunology · 2025
    Article
  7. T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025
    Review
  8. Transcriptional network dynamics in early T cell development.The Journal of experimental medicine · 2024
    Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Transcriptome-wide subtyping of pediatric and adult T cell acute lymphoblastic leukemia in an international study of 707 cases.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  15. Article
  16. Review
  17. Article
  18. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Ameya ChamphekarDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA;
Sagar S DamleDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA;
George FreedmanDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA;
Sebastian CarottaDivision of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Stephen L NuttDivision of Molecular Immunology, Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, Victoria 3010, Australia.
Ellen V RothenbergDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA; evroth@its.caltech.edu.
California Institute of Technology · USThe University of Melbourne · AU

Funding

LINEAGE COMMITMENT MECHANISMS IN LYMPHOID PRECURSORSR01CA090233 · NCI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI ROTHENBERG, ELLEN V. · 2001 to 2011
$3.9M
Genomic site binding rules and regulatory factor function in developing T cellsR01HD076915 · NICHD · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI ROTHENBERG, ELLEN V. · 2013 to 2017
$2.5M
Key nodes in the T-cell developmental gene regulatory networkR01AI095943 · NIAID · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI ROTHENBERG, ELLEN V. · 2011 to 2015
$2.0M
NCI NIH HHS CA90233NCI NIH HHS R01 CA090233NIAID NIH HHS AI95943NIAID NIH HHS R01 AI095943NICHD NIH HHS HD076915NICHD NIH HHS R01 HD076915
6 · The paper itself

Abstract

The ETS family transcription factor PU.1 is essential for the development of several blood lineages, including T cells, but its function in intrathymic T-cell precursors has been poorly defined. In the thymus, high PU.1 expression persists through multiple cell divisions in early stages but then falls sharply during T-cell lineage commitment. PU.1 silencing is critical for T-cell commitment, but it has remained unknown how PU.1 activities could contribute positively to T-cell development. Here we employed conditional knockout and modified antagonist PU.1 constructs to perturb PU.1 function stage-specifically in early T cells. We show that PU.1 is needed for full proliferation, restricting access to some non-T fates, and controlling the timing of T-cell developmental progression such that removal or antagonism of endogenous PU.1 allows precocious access to T-cell differentiation. Dominant-negative effects reveal that this repression by PU.1 is mediated indirectly. Genome-wide transcriptome analysis identifies novel targets of PU.1 positive and negative regulation affecting progenitor cell signaling and cell biology and indicating distinct regulatory effects on different subsets of progenitor cell transcription factors. Thus, in addition to supporting early T-cell proliferation, PU.1 regulates the timing of activation of the core T-lineage developmental program.

Indexed as

Cell DifferentiationGene Expression Regulation, DevelopmentalAnimalsCells, CulturedCell SurvivalMice, Inbred C57BLProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Receptors, NotchStem CellsT-LymphocytesTrans-ActivatorsTranscriptomeProto-Oncogene ProteinsProto-Oncogene Protein Spi-1Receptors, NotchTrans-Activatorsconditional knockouthematopoiesisin vitro developmentNotchobligate repressorRNA-seq

Identifiers

PMID25846797
PMCPMC4403259
OpenAlexW2098219736

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.