Immune Suppressor Factor Confers Stromal Cell Line with Enhanced Supporting Activity for Hematopoietic Stem Cells.
From: Center of Excellence, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. hnakajim@ims.u-tokyo.ac.jp
Biochemical and biophysical research communications
- Publish Date: Feb 2006
- ISSN: 0006-291X
- Volume: 340
- Issue: 1
- Pages: 35-42
- Medium: Print
- Language: English
- Citation (JAMA): Nakajima Hideaki, Shibata Fumi, Fukuchi Yumi, et al. Immune Suppressor Factor Confers Stromal Cell Line with Enhanced Supporting Activity for Hematopoietic Stem Cells.. Biochem. Biophys. Res. Commun. Feb 2006;340:35-42
Abstract
Immune suppressor factor (ISF) is a subunit of the vacuolar ATPase proton pump. We earlier identified a short form of ISF (ShIF) as a stroma-derived factor that supports cytokine-independent growth of mutant Ba/F3 cells. Here, we report that ISF/ShIF supports self-renewal and expansion of primary hematopoietic stem cells (HSCs). Co-culture of murine bone marrow cells with a stromal cell line overexpressing ISF or ShIF (MS10/ISF or MS10/ShIF) not only enhanced their colony-forming activity and the numbers of long-term culture initiating cells, but also maintained the competitive repopulating activity of HSC. This stem cell supporting activity depended on the proton-transfer function of ISF/ShIF. Gene expression analysis of ISF/ShIF-transfected cell lines revealed down-regulation of secreted frizzled-related protein-1 and tissue inhibitor of metalloproteinase-3, and the restoration of their expressions in MS10/ISF cells partially reversed its enhanced LTC-IC supporting activity to a normal level. These results suggest that ISF/ShIF confers stromal cells with enhanced supporting activities for HSCs by modulating Wnt-activity and the extracellular matrix.
Mesh Headings (Keywords): Animals, Cell Communication, Cell Culture Techniques, Cell Differentiation, Cell Proliferation, Cells, Cultured, Coculture Techniques, Hematopoietic Stem Cells, Mice, Mice, Inbred C57BL, Proton Pumps, Stromal Cells
Check for Full Text / PubMed Unique Identifier (PMID): 16343424
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