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Article
Nature Immunology  4, 457 - 463 (2003)
Published online: 31 March 2003; | doi:10.1038/ni916

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

Hiroo Ueno1, 6, Mao Sakita-Ishikawa1, Yoshihiro Morikawa2, Toru Nakano3, Toshio Kitamura4 & Masaki Saito1, 5

1  Virology Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan.

2  Department of Anatomy and Neurobiology, Wakayama Medical School, Kimiidera, Wakayama 641-8509, Japan.

3  Department of Molecular Cell Biology, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.

4  Division of Cellular Therapy, Advanced Clinical Research Center, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.

5  Department of Oncology and Pharmacodynamics, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan.

6  Present address: Department of Pathology and Developmental Biology, Stanford University School of Medicine, Stanford, CA 94305.

Correspondence should be addressed to Hiroo Ueno hirueno@gan2.res.ncc.go.jp
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.

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Nature Immunology
ISSN: 1529-2908
EISSN: 1529-2916
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