ABIN1 (Q478) is required to prevent hematopoietic deficiencies through regulating type I IFNs expression
A20-binding inhibitor of NF-?B activation (ABIN1) is a polyubiquitin-binding protein that regulates cell death and immune responses. Although Abin1 (Tnip1) is located on chromosome 5q in the region commonly deleted in patients with 5q minus syndrome, the most distinct of the myelodysplastic syndromes (MDSs), the precise role of ABIN1 in MDSs remains unknown. In this study, we generated mice with a mutation that disrupts the polyubiquitin-binding site (Abin1Q478H/Q478H). These mice developed MDS-like diseases characterized by anemia, thrombocytopenia, and megakaryocyte dysplasia. Extramedullary hematopoiesis and bone marrow failure are also observed in Abin1Q478H/Q478H mice.  t Notably, higher levels of type I interferon (IFN-I) expression were observed in the bone marrow cells of Abin1Q478H/Q478H mice than in those of wild-type mice. Consistently, blocking type I IFN signaling through the co-deletion of Ifnar1 greatly ameliorated anemia, thrombocytopenia, and splenomegaly in Abin1Q478H/Q478H mice. Taken together, these results demonstrated that ABIN1 (Q478) prevents the development of hematopoietic deficiencies by regulating type I IFN expression. Overall design: Isolate and amplify bone marrow HSPC cells from mice including HPC-1, HPC-2, MPP, and LT-HSC, and then perform transcriptome sequencing.