Transcriptomic diversity in human medullary thymic epithelial cells.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
02 08 2022
02 08 2022
Historique:
received:
25
10
2021
accepted:
30
06
2022
entrez:
2
8
2022
pubmed:
3
8
2022
medline:
5
8
2022
Statut:
epublish
Résumé
The induction of central T cell tolerance in the thymus depends on the presentation of peripheral self-epitopes by medullary thymic epithelial cells (mTECs). This promiscuous gene expression (pGE) drives mTEC transcriptomic diversity, with non-canonical transcript initiation, alternative splicing, and expression of endogenous retroelements (EREs) representing important but incompletely understood contributors. Here we map the expression of genome-wide transcripts in immature and mature human mTECs using high-throughput 5' cap and RNA sequencing. Both mTEC populations show high splicing entropy, potentially driven by the expression of peripheral splicing factors. During mTEC maturation, rates of global transcript mis-initiation increase and EREs enriched in long terminal repeat retrotransposons are up-regulated, the latter often found in proximity to differentially expressed genes. As a resource, we provide an interactive public interface for exploring mTEC transcriptomic diversity. Our findings therefore help construct a map of transcriptomic diversity in the healthy human thymus and may ultimately facilitate the identification of those epitopes which contribute to autoimmunity and immune recognition of tumor antigens.
Identifiants
pubmed: 35918316
doi: 10.1038/s41467-022-31750-1
pii: 10.1038/s41467-022-31750-1
pmc: PMC9345899
doi:
Substances chimiques
Epitopes
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4296Subventions
Organisme : NCI NIH HHS
ID : P30 CA045508
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI167862
Pays : United States
Organisme : NIH HHS
ID : S10 OD028632
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008444
Pays : United States
Informations de copyright
© 2022. The Author(s).
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