Evidence map›Paper›PMID 31629685›Full record

ArticleCell systems2019

Single-Cell Analysis Reveals Regulatory Gene Expression Dynamics Leading to Lineage Commitment in Early T Cell Development.

Wen Zhou, Mary A Yui, Brian A Williams, Jina Yun, Barbara J Wold, Long Cai, Ellen V Rothenberg

Abstract read
In one paragraph

Article in Cell systems, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.

0numbers the graph read from it
0cells of the map it votes in
68citing 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

68 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025
    Review
  11. Review
  12. Frontiers in immunology · 2025
    Article
  13. Review
  14. Transcriptional network dynamics in early T cell development.The Journal of experimental medicine · 2024
    Review
  15. Thymic epithelial organoids mediate T-cell development.Development (Cambridge, England) · 2024
    Article
  16. Article
  17. T-cell commitment inheritance-an agent-based multi-scale model.NPJ systems biology and applications · 2024
    Article
  18. Article
  19. Article
  20. Review

8 more citing papers are in PubMed but not listed here.

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

7 authors.

Wen ZhouDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Mary A YuiDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Brian A WilliamsDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Jina YunDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Barbara J WoldDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Long CaiDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Ellen V RothenbergDivision of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA. Electronic address: evroth@its.caltech.edu.

Funding

Kinetic modeling and single-cell molecular mechanisms of early T-cell commitmentR01HL119102 · NHLBI · CALIFORNIA INSTITUTE OF TECHNOLOGY · PI PETERSON, CARSTEN, ROTHENBERG, ELLEN V. · 2014 to 2018
$3.0M
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
NHLBI NIH HHS R01 HL119102NICHD NIH HHS R01 HD076915
6 · The paper itself

Abstract

Intrathymic T cell development converts multipotent precursors to committed pro-T cells, silencing progenitor genes while inducing T cell genes, but the underlying steps have remained obscure. Single-cell profiling was used to define the order of regulatory changes, employing single-cell RNA sequencing (scRNA-seq) for full-transcriptome analysis, plus sequential multiplexed single-molecule fluorescent in situ hybridization (seqFISH) to quantitate functionally important transcripts in intrathymic precursors. Single-cell cloning verified high T cell precursor frequency among the immunophenotypically defined "early T cell precursor" (ETP) population; a discrete committed granulocyte precursor subset was also distinguished. We established regulatory phenotypes of sequential ETP subsets, confirmed initial co-expression of progenitor with T cell specification genes, defined stage-specific relationships between cell cycle and differentiation, and generated a pseudotime model from ETP to T lineage commitment, supported by RNA velocity and transcription factor perturbations. This model was validated by developmental kinetics of ETP subsets at population and clonal levels. The results imply that multilineage priming is integral to T cell specification.

Indexed as

Models, ImmunologicalCell DifferentiationCell LineageGene Expression ProfilingGene Expression RegulationGene SilencingIn Situ Hybridization, FluorescencePluripotent Stem CellsSequence Analysis, RNASingle-Cell AnalysisThymus GlandT-Lymphocytesclonal development assaydevelopmental trajectorymodel validationmultilineage primingRNA velocitysingle-cell RNA-seqsingle-molecule in situ hybridizationT cell developmenttranscription factors

Identifiers

PMID31629685
PMCPMC6932747

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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.