Single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells

Abstract Recent advances in single-cell RNA sequencing (scRNA-seq) have improved our understanding of the association between tumor-infiltrating lymphocyte (TILs) heterogeneity and cancer initiation and progression. However, studies investigating alternative splicing (AS) as an important regulatory...

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Autores principales:	Shang Liu, Biaofeng Zhou, Liang Wu, Yan Sun, Jie Chen, Shiping Liu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a72e0578e18e4baa9b5ab6932f921a72
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spelling	oai:doaj.org-article:a72e0578e18e4baa9b5ab6932f921a722021-12-02T13:19:29ZSingle-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells10.1038/s41598-021-84693-w2045-2322https://doaj.org/article/a72e0578e18e4baa9b5ab6932f921a722021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84693-whttps://doaj.org/toc/2045-2322Abstract Recent advances in single-cell RNA sequencing (scRNA-seq) have improved our understanding of the association between tumor-infiltrating lymphocyte (TILs) heterogeneity and cancer initiation and progression. However, studies investigating alternative splicing (AS) as an important regulatory factor of heterogeneity remain limited. Here, we developed a new computational tool, DESJ-detection, which accurately detects differentially expressed splicing junctions (DESJs) between cell groups at the single-cell level. We analyzed 5063 T cells of hepatocellular carcinoma (HCC) and identified 1176 DESJs across 11 T cell subtypes. Interestingly, DESJs were enriched in UTRs, and have putative effects on heterogeneity. Cell subtypes with a similar function closely clustered together at the AS level. Meanwhile, we identified a novel cell state, pre-activation with the isoform markers ARHGAP15-205. In summary, we present a comprehensive investigation of alternative splicing differences, which provided novel insights into T cell heterogeneity and can be applied to other full-length scRNA-seq datasets.Shang LiuBiaofeng ZhouLiang WuYan SunJie ChenShiping LiuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Shang Liu Biaofeng Zhou Liang Wu Yan Sun Jie Chen Shiping Liu Single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells
description	Abstract Recent advances in single-cell RNA sequencing (scRNA-seq) have improved our understanding of the association between tumor-infiltrating lymphocyte (TILs) heterogeneity and cancer initiation and progression. However, studies investigating alternative splicing (AS) as an important regulatory factor of heterogeneity remain limited. Here, we developed a new computational tool, DESJ-detection, which accurately detects differentially expressed splicing junctions (DESJs) between cell groups at the single-cell level. We analyzed 5063 T cells of hepatocellular carcinoma (HCC) and identified 1176 DESJs across 11 T cell subtypes. Interestingly, DESJs were enriched in UTRs, and have putative effects on heterogeneity. Cell subtypes with a similar function closely clustered together at the AS level. Meanwhile, we identified a novel cell state, pre-activation with the isoform markers ARHGAP15-205. In summary, we present a comprehensive investigation of alternative splicing differences, which provided novel insights into T cell heterogeneity and can be applied to other full-length scRNA-seq datasets.
format	article
author	Shang Liu Biaofeng Zhou Liang Wu Yan Sun Jie Chen Shiping Liu
author_facet	Shang Liu Biaofeng Zhou Liang Wu Yan Sun Jie Chen Shiping Liu
author_sort	Shang Liu
title	Single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells
title_short	Single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells
title_full	Single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells
title_fullStr	Single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells
title_full_unstemmed	Single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells
title_sort	single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating t cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/a72e0578e18e4baa9b5ab6932f921a72
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_version_	1718393289460154368

Single-cell differential splicing analysis reveals high heterogeneity of liver tumor-infiltrating T cells

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