Multimodal human thymic profiling reveals trajectories and cellular milieu for T agonist selection.

T agonist selection T cell development antigen-presenting cells autoimmunity human thymus multi-modal single-cell RNA sequencing spatial transcriptomics

Journal

Frontiers in immunology
ISSN: 1664-3224
Titre abrégé: Front Immunol
Pays: Switzerland
ID NLM: 101560960

Informations de publication

Date de publication:
2022
Historique:
received: 07 11 2022
accepted: 22 12 2022
entrez: 6 2 2023
pubmed: 7 2 2023
medline: 8 2 2023
Statut: epublish

Résumé

To prevent autoimmunity, thymocytes expressing self-reactive T cell receptors (TCRs) are negatively selected, however, divergence into tolerogenic, agonist selected lineages represent an alternative fate. As thymocyte development, selection, and lineage choices are dependent on spatial context and cell-to-cell interactions, we have performed Cellular Indexing of Transcriptomes and Epitopes by sequencing (CITE-seq) and spatial transcriptomics on paediatric human thymu​​s. Thymocytes expressing markers of strong TCR signalling diverged from the conventional developmental trajectory prior to CD4

Identifiants

pubmed: 36741401
doi: 10.3389/fimmu.2022.1092028
pmc: PMC9895842
doi:

Substances chimiques

Receptors, Antigen, T-Cell 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1092028

Informations de copyright

Copyright © 2023 Heimli, Flåm, Hjorthaug, Trinh, Frisk, Dumont, Ribarska, Tekpli, Saare and Lie.

Déclaration de conflit d'intérêts

TR was employed by the company Exact Sciences Innovation Ltd. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Marte Heimli (M)

Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.

Siri Tennebø Flåm (ST)

Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.

Hanne Sagsveen Hjorthaug (HS)

Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.

Don Trinh (D)

Department of Pathology, Oslo University Hospital, Oslo, Norway.

Michael Frisk (M)

Institute for Experimental Medical Research, Oslo University Hospital, University of Oslo, Oslo, Norway.
KG Jebsen Centre for Cardiac Research, University of Oslo, Oslo, Norway.

Karl-Andreas Dumont (KA)

Department of Cardiothoracic Surgery, Oslo University Hospital, Oslo, Norway.

Teodora Ribarska (T)

Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.

Xavier Tekpli (X)

Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.

Mario Saare (M)

Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.

Benedicte Alexandra Lie (BA)

Department of Medical Genetics, Oslo University Hospital, University of Oslo, Oslo, Norway.

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