Combined effects of Notch signaling and cytokines induce a multiple log increase in precursors with lymphoid and myeloid reconstituting ability

Blood - Tập 101 Số 5 - Trang 1784-1789 - 2003
Barbara Varnum‐Finney1,2, Carolyn Brashem‐Stein1,2, Irwin D. Bernstein1,2
1From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and the Department of Pediatrics, University of Washington, Seattle.
2the Department of Pediatrics, University of Washington, Seattle.

Tóm tắt

We investigated whether combined signaling induced by engineered Notch ligands and hematopoietic growth factors influences hematopoietic stem-cell differentiation. We show that incubation of murine marrow precursors with Delta1ext-IgG, a Notch ligand consisting of the Delta1 extracellular domain fused to the Fc portion of human immunoglobulin G1 (IgG1), and growth factors stem cell factor (SCF), interleukin 6 (IL-6), IL-11, and Flt3-l inhibited myeloid differentiation and promoted a several-log increase in the number of precursors capable of short-term lymphoid and myeloid repopulation. Addition of IL7 promoted early T-cell development, whereas addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) led to terminal myeloid differentiation. These results support a role for combinatorial effects by Notch and cytokine-induced signaling pathways in regulating hematopoietic cell fate and suggest the usefulness of Notch ligand in increasing hematopoietic precursor numbers for clinical stem-cell transplantation.

Từ khóa


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Blood

Tập 101 Số 5

1784-1789

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