Evidence map›Paper›PMID 34331993›Full record

ArticleThe Journal of allergy and clinical immunology2022

Generation of functional human thymic cells from induced pluripotent stem cells.

Stephan A Ramos, John J Morton, Prabha Yadav, Brendan Reed, Sheila I Alizadeh, Ali H Shilleh, Loni Perrenoud, James Jaggers, John Kappler, Antonio Jimeno and 1 more

Open access · greenAbstract read
In one paragraph

Article in The Journal of allergy and clinical immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.8field-weighted citation impact, top 14% of its field
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

24 citing papers in PubMed, 30 citations in OpenAlex.

  1. Article
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  6. Article
  7. Review
  8. Article
  9. Informed clinical decisions by outfoxing human FOXN1 variants.The Journal of allergy and clinical immunology · 2025
    Review
  10. Article
  11. Article
  12. Review
  13. Thymic epithelial organoids mediate T-cell development.Development (Cambridge, England) · 2024
    Article
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Inborn errors of immunity associated with defects of thymic development.Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology · 2022
    Review
  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

11 authors at 3 institutions in 1 country.

Stephan A RamosBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colo.
John J MortonDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colo.
Prabha YadavBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colo.
Brendan ReedBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colo; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colo.
Sheila I AlizadehBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colo.
Ali H ShillehBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colo.
Loni PerrenoudDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colo.
James JaggersSurgery-Cardiothoracic Department, University of Colorado School of Medicine, Aurora, Colo.
John KapplerBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colo; Department of Biomedical Research, National Jewish Health, Denver, Colo.
Antonio JimenoDivision of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, Colo; Charles C. Gates Center for Regenerative Medicine, University of Colorado School of Medicine, Aurora, Colo. Electronic address: antonio.jimeno@cuanschutz.edu.
Holger A RussBarbara Davis Center for Diabetes, University of Colorado Anschutz Medical Campus, Aurora, Colo; Charles C. Gates Center for Regenerative Medicine, University of Colorado School of Medicine, Aurora, Colo. Electronic address: holger.russ@cuanschutz.edu.
University of Colorado Anschutz Medical Campus · USUniversity of Colorado Denver · USNational Jewish Health · US

Funding

University of Colorado Anschutz Medical Campus DRCP30DK116073 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI PETER J DEMPSEY · 2020 to 2026
$10.8M
Targeting PD-L1 interactome signaling to enhance immunotherapy efficacy in head and neck squamous cell cancerR01CA149456 · NCI · UNIVERSITY OF COLORADO DENVER · PI Antonio Jimeno · 2010 to 2026
$5.6M
Training in Translational Research of Skin DiseasesT32AR007411 · NIAMS · UNIVERSITY OF COLORADO DENVER · PI ASGARI, MARYAM MANDANA, ROOP, DENNIS · 1986 to 2025
$4.8M
Molecular Mechanisms of Immune ToleranceT32AI074491 · NIAID · NATIONAL JEWISH HEALTH · PI CAMBIER, JOHN C, PELANDA, ROBERTA · 2009 to 2023
$4.1M
Predoctoral Training Program in Molecular and Cellular Biology (Supplement: Mentoring in the Research Environment)T32GM136444 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI MICHAEL A MCMURRAY, Rytis Prekeris · 2020 to 2026
$3.7M
Predoctoral Training Program in Molecular BiologyT32GM008730 · NIGMS · UNIVERSITY OF COLORADO DENVER · PI PREKERIS, RYTIS, SCLAFANI, ROBERT A · 1999 to 2019
$3.3M
Development of an autologous humanized model of melanoma exploring human thymic education capacityR01CA213102 · NCI · UNIVERSITY OF COLORADO DENVER · PI JIMENO, ANTONIO · 2017 to 2019
$1.7M
Improving human pluripotent stem cell derived beta cell transplantation using genetic lineage tracing.R01DK120444 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI RUSS, HOLGER A. · 2018 to 2021
$1.5M
Interdisciplinary Bioengineering Research Training in DiabetesT32DK120520 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI Richard KP Benninger, KATHRYN M HASKINS · 2020 to 2026
$1.1M
Stress induced changes to the human beta cell proteomeR21AI140044 · NIAID · UNIVERSITY OF COLORADO DENVER · PI DAVIDSON, HOWARD W, RUSS, HOLGER A. · 2019 to 2020
$428k
NCI NIH HHS R01 CA149456NCI NIH HHS R01 CA213102NIAID NIH HHS R21 AI140044NIAID NIH HHS T32 AI074491NIAMS NIH HHS T32 AR007411NIDDK NIH HHS P30 DK116073NIDDK NIH HHS R01 DK120444NIDDK NIH HHS T32 DK120520NIGMS NIH HHS T32 GM008730NIGMS NIH HHS T32 GM136444
6 · The paper itself

Abstract

backgroundThe thymus is a glandular organ that is essential for the formation of the adaptive immune system by educating developing T cells. The thymus is most active during childhood and involutes around the time of adolescence, resulting in a severe reduction or absence of naive T-cell output. The ability to generate a patient-derived human thymus would provide an attractive research platform and enable the development of novel cell therapies.

objectivesThis study sought to systematically evaluate signaling pathways to develop a refined direct differentiation protocol that generates patient-derived thymic epithelial progenitor cells from multiple induced pluripotent stem cells (iPSCs) that can further differentiate into functional patient-derived thymic epithelial cells on transplantation into athymic nude mice.

methodsDirected differentiation of iPSC generated TEPs that were transplanted into nude mice. Between 14 and 19 weeks posttransplantation, grafts were removed and analyzed by flow cytometry, quantitative PCR, bulk RNA sequencing, and single-cell RNA sequencing for markers of thymic-cell and T-cell development.

resultsA direct differentiation protocol that allows the generation of patient-derived thymic epithelial progenitor cells from multiple iPSC lines is described. On transplantation into athymic nude mice, patient-derived thymic epithelial progenitor cells further differentiate into functional patient-derived thymic epithelial cells that can facilitate the development of T cells. Single-cell RNA sequencing analysis of iPSC-derived grafts shows characteristic thymic subpopulations and patient-derived thymic epithelial cell populations that are indistinguishable from TECs present in primary neonatal thymus tissue.

conclusionsThese findings provide important insights and resources for researchers focusing on human thymus biology.

Indexed as

AnimalsCell DifferentiationCells, CulturedEpithelial CellsHumansInduced Pluripotent Stem CellsMiceSequence Analysis, RNAThymus GlandT-Lymphocytesdirect differentiationHuman neonatal thymuspatient derived induced pluripotent stem cellssingle-cell RNA sequencingthymic epithelial cellsthymic epithelial progenitors

Identifiers

PMID34331993
PMCPMC8815270
OpenAlexW3183165098

What OpenQuestion holds

Textmetadata
LicenceTDM
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.