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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URL: https://www.ncbi.nlm.nih.gov/pubmed/35918316
DOI: 10.1038/s41467-022-31750-1

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: 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
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transcriptomes
CSHL Authors:
Communities: CSHL labs > Meyer Lab
CSHL labs > Schorn lab
SWORD Depositor: CSHL Elements
Depositing User: CSHL Elements
Date: 2 August 2022
Date Deposited: 23 Aug 2022 02:18
Last Modified: 23 Aug 2022 02:18
PMCID: PMC9345899
URI: https://repository.cshl.edu/id/eprint/40698

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