DDX41 is needed for pre- and postnatal hematopoietic stem cell differentiation in mice.

ABSTRACT: DDX41 is a tumor suppressor frequently mutated in human myeloid neoplasms, but whether it affects hematopoiesis is unknown. Using a knockout mouse, we demonstrate that DDX41 is required for mouse hematopoietic stem and progenitor cell (HSPC) survival and differentiation, particularly of myeloid lineage cells. Transplantation of Ddx41 knockout fetal liver and adult bone marrow (BM) cells was unable to rescue mice from lethal irradiation, and knockout stem cells were also defective in colony formation assays. RNA-seq analysis of Lin^-/cKit⁺/Sca1⁺Ddx41 knockout cells from fetal liver demonstrated that the expression of many genes associated with hematopoietic differentiation were altered. Furthermore, differential splicing of genes involved in key biological pr

SUBMITTER: Ma J 

PROVIDER: S-EPMC9023775 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature