A stromal cell-derived membrane protein that supports hematopoietic stem cells

Nat Immunol. 2003 May;4(5):457-63. doi: 10.1038/ni916. Epub 2003 Mar 31.

Abstract

Hematopoietic stem cells cannot be maintained in vitro without stromal cells, even if they are provided with growth factors, and it is likely that supportive cells in the bone marrow express membrane or secreted proteins that maintain hematopoiesis. Here we show that mKirre, a mammalian homolog of the gene kirre of Drosophila melanogaster, encodes a type Ia membrane protein that is involved in the hematopoietic supportive capacity of OP9 mouse stromal cells. Repressing mKirre expression with a short interfering RNA significantly reduced this supportive capacity. Our data suggest that mKirre is cleaved by metalloproteinases and that the extracellular domain of mKirre is responsible for supporting hematopoietic stem cells. These results contribute to our understanding of the mechanisms by which the hematopoietic microenvironment regulates hematopoiesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • COS Cells
  • Cell Division
  • Cell Line
  • Cricetinae
  • DNA, Complementary / genetics
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Gene Expression
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / metabolism*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Metalloendopeptidases / metabolism
  • Mice
  • Molecular Sequence Data
  • Muscle Proteins*
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Stromal Cells / metabolism*

Substances

  • DNA, Complementary
  • Drosophila Proteins
  • Kirrel3 protein, mouse
  • Membrane Proteins
  • Muscle Proteins
  • kirre protein, Drosophila
  • Metalloendopeptidases

Associated data

  • GENBANK/AB058770
  • GENBANK/AF196553