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bioRxiv · 10.1101/2020.07.22.215855

Single-cell Long Non-coding RNA Landscape of T Cells in Human Cancer Immunity

Luo, H.·Bu, D.·Shao, L.·Li, Y.·Sun, L.·Wang, C.·Wang, J.·Yang, W.·Yang, X.·Dong, J.·Zhao, Y.·Li, F.
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Abstract

The development of new therapeutic targets for cancer immunotherapies and the development of new biomarkers require deep understanding of T cells. To date, the complete landscape and systematic characterization of long noncoding RNAs (lncRNAs) in T cells in cancer immunity are lacking. Here, by systematically analyzing full-length single-cell RNA sequencing (scRNA-seq) data of more than 20,000 T cell libraries across three cancer types, we provide the first comprehensive catalog and the functional repertoires of lncRNAs in human T cells. Specifically, we developed a custom pipeline for de novo transcriptome assembly obtaining 9,433 novel lncRNA genes that increased the number of current human lncRNA catalog by 16% and nearly doubled the number of lncRNAs expressed in T cells. We found that a portion of expressed genes in single T cells were lncRNAs which have been overlooked by the majority of previous studies. Based on metacell maps constructed by MetaCell algorithm that partition scRNA-seq datasets into disjointed and homogenous groups of cells (metacells), 154 signature lncRNAs associated with effector, exhausted, and regulatory T cell states are identified, 84 of which are functionally annotated based on co-expression network, indicating that lncRNAs might broadly participate in regulation of T cell functions. Our findings provide a new point of view and resource for investigating the mechanisms of T cell regulation in cancer immunity as well as for novel cancer-immune biomarker development and cancer immunotherapies.

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Luo, H., Bu, D., Shao, L., Li, Y., Sun, L., Wang, C., Wang, J., Yang, W., Yang, X., Dong, J., Zhao, Y., Li, F.. 2020-07-24. Single-cell Long Non-coding RNA Landscape of T Cells in Human Cancer Immunity. https://doi.org/10.1101/2020.07.22.215855

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