GSE116674
PRMT5 Modulates Splicing in Hematopoietic Stem Cells
This study aimed to clarify the role of PRMT5 in the hematopoietic stem cell (HSC) compartment, and elucidate the functional relevance of PRMT5-mediated splicing in HSCs. We confirm the cell intrinsic requirement for PRMT5 in HSC maintenance, and present evidence suggesting that PRMT5 deficiency perturbs HSC proteostasis. Notably, we also uncover a critical role for PRMT5 in maintaining HSC genomic integrity by modulating splicing of genes involved in DNA repair; loss of which leads to unresolved DNA damage, p53 activation and rapid HSC exhaustion. Overall, these findings establish PRMT5-mediated splicing as a major determinant of HSC fate, and highlight the need to maintain an adequate level of PRMT5 activity in HSCs. Overall design: Hematopoietic stem cells (HSCs; Lineage-Sca-1+CD48-CD150+), isolated from Prmt5fl/fl or Prmt5?/? littermate- and gender-matched mice 7 days post-induction, were subjected to RNA-seq. HSCs for each independent sample were obtained from bone marrow cells pooled from two mice. Three independent samples were obtained for each group.