The Notch ligand, Jagged-1, influences the development of primitive hematopoietic precursor cells

Blood. 1998 Jun 1;91(11):4084-91.

Abstract

We examined the expression of two members of the Notch 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-1(ext)). 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Calcium-Binding Proteins
  • Cell Differentiation
  • Fibroblasts / metabolism
  • Hematopoietic Stem Cells / cytology*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Jagged-1 Protein
  • Ligands
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / metabolism
  • Mice
  • Protein Binding
  • Receptor, Notch1
  • Receptor, Notch2
  • Receptors, Cell Surface / biosynthesis
  • Receptors, Cell Surface / metabolism
  • Serrate-Jagged Proteins
  • Transcription Factors*
  • Transfection

Substances

  • Calcium-Binding Proteins
  • Intercellular Signaling Peptides and Proteins
  • JAG1 protein, human
  • Jag1 protein, mouse
  • Jagged-1 Protein
  • Ligands
  • Membrane Proteins
  • NOTCH1 protein, human
  • NOTCH2 protein, human
  • Notch1 protein, mouse
  • Notch2 protein, mouse
  • Receptor, Notch1
  • Receptor, Notch2
  • Receptors, Cell Surface
  • Serrate-Jagged Proteins
  • Transcription Factors