A Stromal Cell-derived Membrane Protein That Supports Hematopoietic Stem Cells

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.