ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/DRR356/DRR356488/DRR356488.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/DRR356/DRR356486/DRR356486.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/DRR356/DRR356487/DRR356487.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/DRR356/DRR356489/DRR356489.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/DRR356/DRR356485/DRR356485.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/DRR356/DRR356484/DRR356484.fastq.gzprimary200OKGenomicsDivision of Stem Cell and Molecular Medicine, Center for Stem Cell Biology and Regenerative Medicine, Institute of Medical Science, University of Tokyohttps://www.ebi.ac.uk/ena/browser/view/PRJDB13329Mus musculusThe identification of characteristic differences between cancer stem cells and their normal counterparts remains a key challenge for cancer treatment. Here, we investigated the role of immunoglobulin superfamily member 8 (Igsf8, also known as EWI-2, PGRL, and CD316) on normal and malignant hematopoietic stem cells, mainly using the conditional knockout model. Deletion of Igsf8 did not affect steady state hematopoiesis, but it led to a significant improvement of survival in mouse myeloid leukemia models. Deletion of Igsf8 significantly depletes leukemia stem cells (LSCs) through enhanced apoptosis and b-catenin degradation. At a molecular level, we found that activation of b-catenin in LSCs depends on Igsf8, which promotes the association of FZD4 with its co-receptor LRP6 in the presence of Igsf8. Similarly, IGSF8 inhibition blocks the colony-forming ability of LSCs and improves the survival of recipients in xenograft models of myeloid leukemia. Collectively, these data indicate strong genetic evidence identifying Igsf8 as a key regulator of myeloid leukemia and the possibility that targeting IGSF8 may serve as a new therapeutic approach against myeloid leukemia.ENAMus musculus, Laboratory Mice., House, Mus, Laboratory, Swiss, Mus domesticus, mouse, Mus musculus domesticus, Swiss Mouse, mouse <Mus musculus>, Mouse, House Mice, Swiss Mice, house mouse, Mice, Laboratory Mouse, House Mouse, mice C57BL/6xCBA/CaJ hybrid, domesticus, Mus muscarisMyelogenous Leukemias, Myelocytic, biochemical pathways, Myelogenous, leukemia, single-organism catabolic process, multicellular organismal catabolic process, cellular breakdown, Colony Forming Unit, leukemia granulocytic, Granulocytic Leukemias, Immunoglobulin, degradation, Myeloid, leukemia myelogenous, malignant, Globulin, Monocytic, Monocytic Leukemia, Progenitor Cells, Colony-Forming Units, Immune Globulin, Progenitor Cell, Myelocytic Leukemia, myelocytic leukaemia, Immune Globulins, Leukemias, Cell, Catenin, cellular catabolism, antibody, Chronic Monocytic Leukemias, non-lymphocytic leukemia, Colony-Forming Unit, Chronic Monocytic Leukemia, Stem Cell, Catenin Protein, Myeloid Leukemias, leukemia myeloid, Protein, Mother Cells, cellular degradation, secretion, Progenitor, non-lymphoblastic leukemia, myeloid granulocytic leukemia, opsonin activity, myeloid leukemia, Mother Cell, Chronic Monocytic, myelogenous leukaemia, Leukemia, breakdown, biodegradation, myeloid leukaemia, breakdown of molecule., leukaemia granulocytic, breakdown of chemical, catabolism, Stem, Granulocytic Leukemia, non-lymphoblastic leukaemia, granulocytic, Mother, Myelogenous Leukemia, Colony Forming Units, myeloid granulocytic leukaemia, leukaemia myelogenous, myelocytic leukemia, Granulocytic, immunoglobulin, breakdown of substance, Immune, non-lymphocytic leukaemia, leukaemia myeloid, Catenin Proteins, Cells, Myelocytic Leukemias, Myeloid Leukemia, B cell receptor activity, Chronic, biotransformation, Globulins, myelogenous leukemia, Non-Lymphocytic Leukemia, Monocytic LeukemiasfalseMus musculusImmunoglobulin superfamily member 8 maintains myeloid leukemia stem cells through inhibition of b-catenin degradation2025-09-242022-04-20PRJDB1332910090