Landscape of transcript isoforms in single T cells infiltrating in non-small-cell lung cancer

Jiesheng Li; Hannah Y. Comeau; Zemin Zhang; Xianwen Ren

doi:10.1016/j.jgg.2020.06.006

Volume 47 Issue 7

Jul. 2020

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Article Navigation > Journal of Genetics and Genomics > 2020 > 47(7): 373-388

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Landscape of transcript isoforms in single T cells infiltrating in non-small-cell lung cancer

doi: 10.1016/j.jgg.2020.06.006

a
Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China
b
BIOPIC, Beijing Advanced Innovation Center for Genomics, School of Life Sciences, Peking University, Beijing, 100871, China

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Corresponding author: E-mail address: zemin@pku.edu.cn (Zemin Zhang); E-mail address: renxwise@pku.edu.cn (Xianwen Ren)
Publish Date: 2020-07-25

Abstract

Abstract

Single-cell RNA sequencing (scRNA-seq) has enabled high-resolution characterization of molecular signatures of tumor-infiltrating lymphocytes. However, analyses at the transcript isoform level are rarely reported. As alternative splicing is critical to T-cell differentiation and activation, here, we proposed a computational method named IDEA (Isoform Detection, Enrichment, and functional Annotation) to comprehensively detect and annotate differentially used isoforms across cell subtypes. We applied IDEA on a scRNA-seq data set of 12,346 T cells from non-small-cell lung cancer (NSCLC). We found that most genes tend to dominantly express one isoform in single T cells, enabling typing T cells based on the isotypes, given a gene. Isotype analysis suggested that tumor-infiltrating T cells significantly preferred specific isotypes for 245 genes in CD8⁺ T cells and 456 genes in CD4⁺ T cells. Functional annotation suggests that the preferred isoforms involved in coding/noncoding switches, transcription start site changes, gains/losses of domains, and subcellular translocation. Clonal analysis revealed that isoform switching occurred during T-cell activation/differentiation. Our analysis provides precise characterization of the molecular events in tumor-infiltrating T cells and sheds new light on the regulatory mechanisms of tumor-infiltrating T cells.
- Alternative splicing,
- T-cell subtypes,
- Single-cell,
- RNA-seq

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References(56)

References

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