Transcriptomic diversity in human medullary thymic epithelial cells

Carter, Jason A, Strömich, Léonie, Peacey, Matthew, Chapin, Sarah R, Velten, Lars, Steinmetz, Lars M, Brors, Benedikt, Pinto, Sheena, Meyer, Hannah V (August 2022) Transcriptomic diversity in human medullary thymic epithelial cells. Nature Communications, 13 (1). p. 4296. ISSN 2041-1723

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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.

Item Type:	Paper
Subjects:	bioinformatics bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > cell differentiation organs, tissues, organelles, cell types and functions > cell types and functions > cell functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell functions > differentiation organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cell organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions > cell types and functions > cell types > epithelial cells organs, tissues, organelles, cell types and functions bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:	Carter, Jason A Meyer, Hannah V. Peacey, Matthew
Communities:	CSHL Cancer Center Program CSHL Cancer Center Program > Cancer Genetics and Genomics Program CSHL labs > Meyer Lab CSHL labs > Schorn lab School of Biological Sciences > Publications
SWORD Depositor:	CSHL Elements
Depositing User:	CSHL Elements
Date:	2 August 2022
Date Deposited:	23 Aug 2022 02:18
Last Modified:	29 Feb 2024 18:07
PMCID:	PMC9345899
URI:	https://repository.cshl.edu/id/eprint/40698

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