NOTCH LIGAND DELTA-1 AND HEMATOPOIESIS

Sloan-Kettering Institute For Cancer Res, New York NY

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Abstract

An important question of hematopoiesis is how a hematopoietic environment maintains hematopoietic stem cells (HSCs). Ex vivo expansion of HSCs for bone marrow transplantation requires HSCs be preserved as well as possible. However, none single cytokine or cytokine combination for ex vivo expansion is optimal in this respect. It is known that cell-cell contact is essential for long-term survival of HSCs. Membrane bound proteins Delta protein and Notch can regulate cell differentiation in many developmental processes. This proposal is to study the role of human Delta-1 that expressed in bone marrow endothelial cells in regulating the self-renewal, differentiation and adhesion of HSCs. Stromal cell lines that overexpress human Delta-1, and the functional DSL of Delta-1 expressed as a recombinant protein, will be used to study the role of human Delta-1 in ex vivo expansion and long term culture of HSCs. This study may provide important information and novel methods to improve ex vivo expansion for bone marrow transplantation and gene therapy.