single-cell transcriptomic analysis of mouse haematopoietic stem cells upon Nat10 deletion

Epigenetic regulation exerts a crucial role in maintaining the balance between self-renewal and differentiation of hematopoietic stem cells (HSCs), thereby sustaining normal hematopoiesis. Although emerging evidence has demonstrated the contribution of RNA N4-acetylcytidine (ac4C) modification and its catalytic enzyme Nat10 to numerous biological processes, particularly tumorigenesis, the landscape and function of ac4C in normal hematopoiesis remain unexplored. In this study, we characterize the landscape of ac4C across the hierarchy of hematopoietic stem and progenitor cells (HSPCs) tracked by single-cell transcriptomic analysis and reveal a key role of Nat10 in the maintenance of HSCs. Overall design: To investigate the role of Nat10-mediated ac4C in HSC maintenance and differentiation, we performed 10×Genomics single-cell RNA sequencing (scRNA-seq) on sorted lineage-negative cells (HSPCs) from the bone marrow (BM) of five independent WT or Nat10 cKO mice.