Keizo Kato

Publications (2)23.75 Total impact

• Article: Notch target Hes5 ensures appropriate Notch induced T- versus B-cell choices in the thymus.

  Barbara Varnum-Finney, Mari H Dallas, Keizo Kato, Irwin D Bernstein
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  ABSTRACT: Notch signaling establishes boundaries in the thymus by inducing T-cell commitment and inhibiting a B-cell choice. Here, we show a significant 1.6-fold increased generation of B-cell precursors in thymuses from mice deficient for Notch target Hes5 compared with wild-type littermates. We further show that culture of bone marrow-derived progenitors with increasing densities of purified immobilized Notch ligand (Delta1(ext-IgG)) induced increased expression of Notch targets Hes1 and Hes5, and that although Hes5-deficient progenitors responded appropriately to high densities of ligand, they misread intermediate and low densities. Together, our results suggest that to ensure an appropriate outcome in the thymus in response to a lower threshold of induced Notch signaling, induction of the additional target Hes5 is required.
  Blood 04/2008; 111(5):2615-20. · 9.90 Impact Factor
• Source

  Available from: PubMed Central

  Article: Density of the Notch ligand Delta1 determines generation of B and T cell precursors from hematopoietic stem cells.

  Mari H Dallas, Barbara Varnum-Finney, Colleen Delaney, Keizo Kato, Irwin D Bernstein
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  ABSTRACT: Notch signaling regulates multiple cell fate decisions by hematopoietic precursors. To address whether different amounts of Notch ligand influence lineage choices, we cultured murine bone marrow lin(-)Sca-1(+)c-kit+ cells with increasing densities of immobilized Delta1(ext-IgG) consisting of the extracellular domain of Delta1 fused to the Fc domain of human IgG1. We found that relatively lower densities of Delta1(ext-IgG) enhanced the generation of Sca-1(+)c-kit+ cells, Thy1(+)CD25+ early T cell precursors, and B220(+)CD43(-/lo) cells that, when cocultured with OP9 stroma cells, differentiated into CD19+ early B cell precursors. Higher densities of Delta1(ext-IgG) also enhanced the generation of Sca-1(+)c-kit+ precursor cells and promoted the development of Thy1(+)CD25+ cells, but inhibited the development of B220(+)CD43(-/lo) cells. Analyses of further isolated precursor populations suggested that the enhanced generation of T and B cell precursors resulted from the effects on multipotent rather than lymphoid-committed precursors. The results demonstrate the density-dependent effects of Delta1 on fate decisions of hematopoietic precursors at multiple maturational stages and substantiate the previously unrecognized ability of Delta1 to enhance the development of both early B and T precursor cells.
  Journal of Experimental Medicine 06/2005; 201(9):1361-6. · 13.85 Impact Factor