The Journal of Experimental Medicine
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Published online 25 April 2005 doi:10.1084/jem.20042450
Rockefeller University Press, 0022-1007 $8.00
JEM, Volume 201, Number 9, 1361-1366
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BRIEF DEFINITIVE REPORT

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

Mari H. Dallas1,2, Barbara Varnum-Finney1, Colleen Delaney1,2, Keizo Kato1, and Irwin D. Bernstein1,2

1 Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
2 Department of Pediatrics, University of Washington, Seattle, WA 98195

CORRESPONDENCE Irwin D. Bernstein: ibernste{at}fhcrc.org

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 Delta1ext-IgG consisting of the extracellular domain of Delta1 fused to the Fc domain of human IgG1. We found that relatively lower densities of Delta1ext-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 Delta1ext-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.


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