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.

doi:http://dx.doi.org/10.1038/s41467-022-31750-1

Transcriptomic diversity in human medullary thymic epithelial cells

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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

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.