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Transcriptomic diversity in human medullary thymic epithelial cells

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dc.contributor.author Carter, Jason A.
dc.contributor.author Strömich, Léonie
dc.contributor.author Peacey, Matthew
dc.contributor.author Chapin, Sarah R.
dc.contributor.author Velten, Lars
dc.contributor.author Steinmetz, Lars M.
dc.contributor.author Brors, Benedikt
dc.contributor.author Pinto, Sheena
dc.contributor.author Meyer, Hannah V.
dc.date.accessioned 2022-11-07T07:30:23Z
dc.date.available 2022-11-07T07:30:23Z
dc.date.issued 2022
dc.identifier.citation Carter JA, Strömich L, Peacey M, Chapin SR, Velten L, Steinmetz LM, Brors B, Pinto S, Meyer HV. Transcriptomic diversity in human medullary thymic epithelial cells. Nat Commun. 2022 Aug 2;13(1):4296. DOI: 10.1038/s41467-022-31750-1
dc.identifier.issn 2041-1723
dc.identifier.uri http://hdl.handle.net/10230/54719
dc.description.abstract 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.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Nature Research
dc.relation.ispartof Nat Commun. 2022 Aug 2;13(1):4296
dc.rights © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
dc.rights.uri http://creativecommons.org/licenses/by/4.0/
dc.title Transcriptomic diversity in human medullary thymic epithelial cells
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1038/s41467-022-31750-1
dc.subject.keyword Central tolerance
dc.subject.keyword Data integration
dc.subject.keyword Gene expression
dc.subject.keyword Transcriptomics
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


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