Evidence map›Paper›PMID 37399024›Full record

ArticleThe Journal of experimental medicine2023

Hnf4 activates mimetic-cell enhancers to recapitulate gut and liver development within the thymus.

Daniel A Michelson, Chong Zuo, Michael Verzi, Christophe Benoist, Diane Mathis

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2023. 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
3.9field-weighted citation impact, top 6% 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, 24 citations in OpenAlex.

  1. Article
  2. Article
  3. Runx3 instructs AireJournal of autoimmunity · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Sterile production of interferons in the thymus.Journal of immunology (Baltimore, Md. : 1950) · 2025
    Review
  11. Review
  12. Article
  13. Review
  14. Article
  15. T Cell Development: From T-Lineage Specification to Intrathymic Maturation.Advances in experimental medicine and biology · 2025
    Review
  16. Review
  17. Rediscovering the human thymus through cutting-edge technologies.The Journal of experimental medicine · 2024
    Review
  18. The partitioning of TCR repertoires by thymic selection.The Journal of experimental medicine · 2024
    Review
  19. Thymic Mimetic Cells: Ontogeny as Immunology.Annual review of cell and developmental biology · 2024
    Review
  20. Aire in Autoimmunity.Annual review of immunology · 2024
    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

5 authors at 2 institutions in 1 country.

Daniel A MichelsonDepartment of Immunology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-9434-5207
Chong ZuoDepartment of Immunology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0001-6117-6438
Michael VerziDepartment of Genetics, Human Genetics Institute of New Jersey, Rutgers University, Piscataway, NJ, USA.ORCID 0000-0003-4082-4330
Christophe BenoistDepartment of Immunology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-1172-6555
Diane MathisDepartment of Immunology, Harvard Medical School, Boston, MA, USA.ORCID 0000-0002-6110-4626
Harvard University · USRutgers, The State University of New Jersey · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
AIRE, a zinc-finger protein that controls autoimmunityR01DK060027 · NIDDK · JOSLIN DIABETES CENTER · PI DIANE J MATHIS · 2002 to 2026
$7.4M
The molecular mechanism of Aire: partnering with DNA-PKR01AI088204 · NIAID · HARVARD MEDICAL SCHOOL · PI DIANE J MATHIS · 2011 to 2026
$5.7M
Mechanisms Driving Metabolic Shifts in the Intestinal EpitheliumR01DK126446 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI VERZI, MICHAEL P. · 2021 to 2025
$2.1M
Mechanisms of Intestinal Epithelial DifferentiationR01DK121915 · NIDDK · RUTGERS, THE STATE UNIV OF N.J. · PI ELLISON, CHRISTOPHER EUGENE, VERZI, MICHAEL P. · 2020 to 2023
$1.7M
NIAID NIH HHS R01 AI088204NIDDK NIH HHS R01 DK060027NIDDK NIH HHS R01 DK121915NIDDK NIH HHS R01 DK126446NIGMS NIH HHS T32 GM007753NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

Mimetic cells are medullary thymic epithelial cells (mTECs) that mimic extra-thymic cell types to tolerize T cells to self-antigens. Here, we dissected the biology of entero-hepato mTECs, mimetic cells expressing gut- and liver-associated transcripts. Entero-hepato mTECs conserved their thymic identity yet accessed wide swaths of enterocyte chromatin and transcriptional programs via the transcription factors Hnf4α and Hnf4γ. Deletion of Hnf4α and Hnf4γ in TECs ablated entero-hepato mTECs and downregulated numerous gut- and liver-associated transcripts, with a primary contribution from Hnf4γ. Loss of Hnf4 impaired enhancer activation and CTCF redistribution in mTECs but did not impact Polycomb-mediated repression or promoter-proximal histone marks. By single-cell RNA sequencing, Hnf4 loss produced three distinct effects on mimetic cell state, fate, and accumulation. Serendipitously, a requirement for Hnf4 in microfold mTECs was discovered, which exposed a requirement for Hnf4γ in gut microfold cells and the IgA response. Study of Hnf4 in entero-hepato mTECs thus revealed mechanisms of gene control in the thymus and periphery alike.

Indexed as

Epithelial CellsHepatocyte Nuclear Factor 4Thymus GlandCell DifferentiationGene Expression RegulationT-LymphocytesTranscription FactorsHepatocyte Nuclear Factor 4Transcription Factors

Identifiers

PMID37399024
PMCPMC10318407
OpenAlexW4382919142

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.