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

First Author  Ma J Year  2022
Journal  Stem Cell Reports Volume  17
Issue  4 Pages  879-893
PubMed ID  35303436 Mgi Jnum  J:326717
Mgi Id  MGI:7264055 Doi  10.1016/j.stemcr.2022.02.010
Citation  Ma J, et al. (2022) DDX41 is needed for pre- and postnatal hematopoietic stem cell differentiation in mice. Stem Cell Reports 17(4):879-893
abstractText  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 processes was observed. Our data reveal a critical role for DDX41 in HSPC differentiation and myeloid progenitor development, likely through regulating gene expression programs and splicing.
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