The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep understanding of Tcells.To date,the complete landscape and systematic characterization of long noncoding RNAs(lncRNAs)i...The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep understanding of Tcells.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.展开更多
基金This work was supported by the Science and Technology Project of Shenzhen,China(Grant Nos.JCYJ20190807145013281,JHZ20170310090257380,JCYJ20170413092711058,and JCYJ20170307095822325)the China Postdoctoral Science Foundation(Grant No.2019M663369)the National Natural Science Foundation of China(Grant No.31970636).
文摘The development of new biomarkers or therapeutic targets for cancer immunotherapies requires deep understanding of Tcells.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.
