title: A stromal cell-derived membrane protein that supports hematopoietic stem cells.
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.
authors.affiliation: Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan. hirueno@gan2.res.ncc.go.jp
authors.forename: Hiroo
authors.initials: H
authors.lastname: Ueno
authors.forename: Mao
authors.initials: M
authors.lastname: Sakita-Ishikawa
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
authors.forename: Masaki
authors.initials: M
authors.lastname: Saito
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D019556:COS Cells; D002455:Cell Division; D002460:Cell Line; D006224:Cricetinae; D018076:DNA, Complementary / Q000235:genetics; D029721:Drosophila Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006410:Hematopoiesis / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009124:Muscle Proteins; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D017154:Stromal Cells / Q000378:metabolism*
chemical_list: D018076:DNA, Complementary; D029721:Drosophila Proteins; C474214:Kirrel3 protein, mouse; D008565:Membrane Proteins; D009124:Muscle Proteins; C413082:kirre protein, Drosophila; D008666:Metalloendopeptidases