Single-cell profiling of long non-coding RNAs in the hematopoietic system.

Long non-coding RNAs (lncRNAs) play a crucial role in normal and dysregulated hematopoiesis. However, the functional repertoire of lncRNAs across various hematopoietic cell types remains elusive. In this study, we constructed a comprehensive single-cell lncRNA atlas containing 207,113 cells, spanning hematopoietic stem and progenitor cells (HSPCs) to differentiated blood cells, by integrating nine single-cell RNA sequencing (scRNA-seq) datasets derived from 30 healthy donors. The hematopoietic hierarchy based on lncRNA expression was highly consistent with that based on protein-coding genes. We identified 3,463 lineage-specific lncRNAs in HSPCs, neutrophils, monocytes, B cells, and T/natural killer cells; 23 of 30 selected lncRNAs were experimentally validated. Importantly, upregulated lncRNAs in pediatric patients with B cell acute lymphoblastic leukemia, T cell acute lymphoblastic leukemia, and acute myeloid leukemia were primarily associated with oxygen response and immune regulation, indicating the potential contribution of lncRNAs to leukemogenesis. In conclusion, our results portray the landscape of lncRNAs in the hematopoietic system, revealing the functional significance of lncRNAs in both normal and abnormal hematopoiesis and providing potential therapeutic targets for the clinical treatment of leukemia.