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

• 作 者: Haitao Luo Dechao Bu Lijuan Shao Yang Li Liang Sun Ce Wang Jing Wang Wei Yang Xiaofei Yang Jun Dong Yi Zhao Furong Li
• 机 构: Translational Medicine Collaborative Innovation Center,The Second Clinical Medical College(Shenzhen
• 出 处: 基因组蛋白质组与生物信息学报（英文版）
• 发表日期: 2021年3期
• 关键词: Long non-coding RNA Transcriptome assembly Metacell Immune regulation Functional

The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep under-standing 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 libraries of T cells across three cancer types, we provided 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 and obtained a novel lncRNA catalog containing 9433 genes. This 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 had been overlooked by the majority of previous studies. Based on metacell maps constructed by the MetaCell algorithm that partitions scRNA-seq datasets into disjointed and homogenous groups of cells (metacells), 154 signature lncRNA genes were identified. They were associated with effector, exhausted, and regulatory T cell states. Moreover, 84 of them were functionally annotated based on the co-expression networks, indicating that lncRNAs might broadly participate in the 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.