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Nat Immunol ; 4(5): 457-63, 2003 May.
Article in English | MEDLINE | ID: mdl-12665856

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.


Subject(s)
Hematopoietic Stem Cells/cytology , Hematopoietic Stem Cells/metabolism , Membrane Proteins/metabolism , Muscle Proteins , Stromal Cells/metabolism , 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 , Membrane Proteins/chemistry , Membrane Proteins/genetics , Metalloendopeptidases/metabolism , Mice , Molecular Sequence Data , Protein Structure, Tertiary , Sequence Homology, Amino Acid
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