Stromal Cell CD9 Regulates Differentiation of Hematopoietic stem/progenitor Cells

Blood. 1999 Apr 15;93(8):2586-94.

Abstract

CD9 belongs to the transmembrane 4 superfamily, and has been shown to influence cell proliferation, motility, and adhesion. We show here that ligation of CD9 modifies proliferation and/or differentiation of hematopoietic stem/progenitors. Pluripotent EML-C1 hematopoietic cells were cocultured with MS-5 stromal cells in the presence of KMC8.8, an anti-CD9 antibody. Numbers of recovered EML-C1 cells were slightly reduced and the antibody caused the hematopoietic cells to migrate beneath the adherent stromal cell layer. Of particular interest, EML-C1 cells recovered from CD9-ligated cultures had undifferentiated properties. Separate pretreatment of the two cell types with antibody showed that stromal-cell CD9 mediated these responses. Spontaneous expression of erythroid marker was completely blocked and there was a shift towards undifferentiated clonogenic progenitors. Immunoprecipitation studies showed that stromal-cell CD9 associates with the beta1 subunit of integrin, as well as a novel 100 kD protein. Antibody cross-linking of cell surface CD9 increased the amount of 100 kD protein that was subsequently coprecipitated with CD9. These observations show that stromal-cell CD9 influences physical interactions with hematopoietic cells and may be one factor that determines the degree of stem cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / physiology*
  • Cell Adhesion
  • Cell Differentiation
  • Chemotaxis
  • Coculture Techniques
  • Erythropoietin / pharmacology
  • Flow Cytometry
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / physiology*
  • Humans
  • Integrin beta1 / physiology
  • Interleukin-3 / pharmacology
  • Membrane Glycoproteins / physiology
  • Mice
  • Recombinant Proteins / pharmacology
  • Stem Cell Factor / pharmacology
  • Stromal Cells / cytology
  • Stromal Cells / physiology*
  • Tetraspanin 29

Substances

  • Antigens, CD
  • CD9 protein, human
  • Cd9 protein, mouse
  • Integrin beta1
  • Interleukin-3
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Stem Cell Factor
  • Tetraspanin 29
  • Erythropoietin