The Notch Ligand, Jagged-1, Influences the Development of Primitive Hematopoietic Precursor Cells

Author:

Varnum-Finney Barbara1,Purton Louise E.1,Yu Monica1,Brashem-Stein Carolyn1,Flowers David1,Staats Steven1,Moore Kateri A.1,Le Roux Isabelle1,Mann Robert1,Gray Grace1,Artavanis-Tsakonas Spyros1,Bernstein Irwin D.1

Affiliation:

1. From the Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; the Department of Pediatrics, The University of Washington, Seattle; the Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, Princeton, NJ; Developmental Genetics Laboratory, Imperial Cancer Research Fund, London, UK; and the Departments of Biology and Cell Biology and Howard Hughes Medical Institute, Yale University, New Haven, CT.

Abstract

Abstract We examined the expression of two members of theNotch family, Notch-1 and Notch-2, and one Notch ligand, Jagged-1, in hematopoietic cells. Both Notch-1 and Notch-2 were detected in murine marrow precursors (Lin−Sca-1+c-kit+). The Notch ligand, Jagged-1, was not detected in whole marrow or in precursors. However, Jagged-1 was seen in cultured primary murine fetal liver stroma, cultured primary murine bone marrow stroma, and in stromal cell lines. These results indicate a potential role for Notch-Notch ligand interactions in hematopoiesis. To further test this possibility, the effect of Jagged-1 on murine marrow precursor cells was assessed by coculturing sorted precursor cells (Lin−Sca-1+c-kit+) with a 3T3 cell layer that expressed human Jagged-1 or by incubating sorted precursors with beads coated with the purified extracellular domain of human Jagged-1 (Jagged-1ext). We found that Jagged-1, presented both on the cell surface and on beads, promoted a twofold to threefold increase in the formation of primitive precursor cell populations. These results suggest a potential use for Notch ligands in expanding precursor cell populations in vitro.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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