Our laboratory studies the molecular and cellular mechanisms underlying the generation of blood cells from hematopoietic stem cells. Hematopoietic stem cells choose either a lymphoid or myeloid lineage pathway at an early stage of differentiation. We have identified and purified immature progenitors on each pathway in mouse bone marrow. Using these highly-purified populations, we are attempting to identify genes involved in activating lineage-specific developmental program. We are also studying the developmental mechanisms of hematopoietic malignancies.
There are three subjects on which we focus:
- The role of cytokine signaling and transcription factors in myelo-lymphoid lineage fate decision
- Developmental mechanisms of allergy-related mast cells and eosinophils
- The role of leukemic fusion genes in malignant transformation at each hematopoietic stage
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Papers & Publications:
- Kondo M, Weissman IL, and Akashi K. Identification of clonogenic common lymphoid progenitors in mouse bone marrow. Cell 91, 661-672, 1997.
- Akashi K, Traver D, Miyamoto T, and Weissman IL. A clonogenic common myeloid progenitor that gives rise to all myeloid lineages. Nature 404, 193-197, 2000.
- Miyamoto T, Iwasaki H, Reizis B, Ye M, Graf T, Weissman IL, and Akashi K. Myeloid or lymphoid promiscuity at the site of hematopoietic lineage decision. Developmental Cell. 3, 137-147, 2002.
- Iwasaki H, Mizuno S, Wells RA, Watanabe S, and Akashi K. GATA-1 converts lymphoid and myelomonocytic progenitors into the megakaryocyte/erythrocyte lineages. Immunity 19, 451-462, 2003.
- Shigematsu H, Reizis B, Iwasaki H, Mizuno S, Hu D, Traver D, Leder P, Sakaguchi N and Akashi K. Plasmacytoid dendritic cells activate lymphoid-specific genetic programs irrespective of their cellular
origin. Immunity 21: 43-53, 2004.
- Opferman JT, Iwasaki H, Ong CC, Suh H, Akashi K, and Korsmeyer S. Obligate role of anti-apoptotic MCL-1 in the survival of hematopoietic stem cells. Science, 2005; 307: 1101-1104.
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