Loss of Tifab, a del(5q) MDS gene, alters hematopoiesis through derepression of Toll-like receptor/TRAF6 signaling

ABSTRACT: TRAF-interacting protein with forkhead-associated domain B (TIFAB) is a haploinsufficient gene in del(5q) Myelodysplastic syndrome (MDS). Hematopoietic-specific deletion of Tifab results in progressive bone marrow (BM) and blood defects, including skewed hematopoietic stem/progenitor cells (HSPC) proportions, altered myeloid differentiation, and progressive cytopenia. A subset of mice transplanted with Tifab knockout (KO) hematopoietic cells develop a bone marrow failure (BMF)-like disease with neutrophil dysplasia and cytopenia. In competitive transplants, Tifab KO HSPC are out-competed by wild-type (WT) cells, suggesting a cell-intrinsic HSPC defect. Gene expression analysis of Tifab KO HSPC identified dysregulation of immune-related signatures, and hypersensitivity to Toll-like receptor

ORGANISM(S): Mus musculus

SUBMITTER: Daniel Starczynowski 

PROVIDER: E-GEOD-72936 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress