Evidence map›Paper›PMID 25224068›Full record

ArticleGenome research2014

Population and single-cell genomics reveal the Aire dependency, relief from Polycomb silencing, and distribution of self-antigen expression in thymic epithelia.

Stephen N Sansom, Noriko Shikama-Dorn, Saule Zhanybekova, Gretel Nusspaumer, Iain C Macaulay, Mary E Deadman, Andreas Heger, Chris P Ponting, Georg A Holländer

Open access · bronzeAbstract read
In one paragraph

Article in Genome research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 227 papers.

0numbers the graph read from it
0cells of the map it votes in
227citing 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

227 citing papers in PubMed, 332 citations in OpenAlex.

  1. Trial
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  6. What Do We Know About Immune System Aging from Human and Animal Studies?International journal of molecular sciences · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Runx3 instructs AireJournal of autoimmunity · 2026
    Article
  11. Review
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  17. Review
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  19. Unexpected heterogeneity and tissue-specific properties of the thymic hematopoietic antigen-presenting cell network.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  20. Article

167 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

9 authors at 3 institutions in 3 countries.

Stephen N SansomMRC Computational Genomics Analysis and Training Programme, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, United Kingdom; stephen.sansom@kennedy.ox.ac.uk stephen.sansom@cantab.net Georg.Hollander@paediatrics.ox.ac.uk Georg-A.Hollaender@unibas.ch.
Noriko Shikama-DornPaediatric Immunology, Department of Biomedicine, University of Basel, and The Basel University Children's Hospital, Basel, 4058, Switzerland;
Saule ZhanybekovaPaediatric Immunology, Department of Biomedicine, University of Basel, and The Basel University Children's Hospital, Basel, 4058, Switzerland;
Gretel NusspaumerPaediatric Immunology, Department of Biomedicine, University of Basel, and The Basel University Children's Hospital, Basel, 4058, Switzerland;
Iain C MacaulayWellcome Trust Sanger Institute-EBI Single Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, United Kingdom;
Mary E DeadmanDevelopmental Immunology, Department of Paediatrics, and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Andreas HegerMRC Computational Genomics Analysis and Training Programme, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, United Kingdom;
Chris P PontingMRC Computational Genomics Analysis and Training Programme, MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, United Kingdom; Wellcome Trust Sanger Institute-EBI Single Cell Genomics Centre, Wellcome Trust Sanger Institute, Hinxton, Cambridge, CB10 1SA, United Kingdom;
Georg A HolländerPaediatric Immunology, Department of Biomedicine, University of Basel, and The Basel University Children's Hospital, Basel, 4058, Switzerland; Developmental Immunology, Department of Paediatrics, and the Weatherall Institute of Molecular Medicine, University of Oxford, Oxford OX3 9DS, United Kingdom.
Boston Children's Hospital · USUniversity of Oxford · GBWellcome Sanger Institute · GB

Funding

Medical Research Council G1000902Medical Research Council MC_EX_G1000902Medical Research Council MC_EX_UU_G1000902Medical Research Council MC_U137761446Medical Research Council MC_UU_12021/1
6 · The paper itself

Abstract

Promiscuous gene expression (PGE) by thymic epithelial cells (TEC) is essential for generating a diverse T cell antigen receptor repertoire tolerant to self-antigens, and thus for avoiding autoimmunity. Nevertheless, the extent and nature of this unusual expression program within TEC populations and single cells are unknown. Using deep transcriptome sequencing of carefully identified mouse TEC subpopulations, we discovered a program of PGE that is common between medullary (m) and cortical TEC, further elaborated in mTEC, and completed in mature mTEC expressing the autoimmune regulator gene (Aire). TEC populations are capable of expressing up to 19,293 protein-coding genes, the highest number of genes known to be expressed in any cell type. Remarkably, in mouse mTEC, Aire expression alone positively regulates 3980 tissue-restricted genes. Notably, the tissue specificities of these genes include known targets of autoimmunity in human AIRE deficiency. Led by the observation that genes induced by Aire expression are generally characterized by a repressive chromatin state in somatic tissues, we found these genes to be strongly associated with H3K27me3 marks in mTEC. Our findings are consistent with AIRE targeting and inducing the promiscuous expression of genes previously epigenetically silenced by Polycomb group proteins. Comparison of the transcriptomes of 174 single mTEC indicates that genes induced by Aire expression are transcribed stochastically at low cell frequency. Furthermore, when present, Aire expression-dependent transcript levels were 16-fold higher, on average, in individual TEC than in the mTEC population.

Indexed as

Gene SilencingAcetylationAIRE ProteinAnimalsAutoantigensChromatinCluster AnalysisComputational BiologyEpithelial CellsGene ExpressionGene Expression ProfilingGene Expression RegulationGene OrderGene TargetingGenetic LociGenetic VectorsAIRE ProteinAutoantigensChromatinHistonesPolycomb-Group ProteinsTranscription Factors

Identifiers

PMID25224068
PMCPMC4248310
OpenAlexW2132003377

What OpenQuestion holds

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LicenceCC BY
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.