title: Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells.
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.
authors.affiliation: 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
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakajima
authors.forename: Fumi
authors.initials: F
authors.lastname: Shibata
authors.forename: Yumi
authors.initials: Y
authors.lastname: Fukuchi
authors.forename: Yuko
authors.initials: Y
authors.lastname: Goto-Koshino
authors.forename: Miyuki
authors.initials: M
authors.lastname: Ito
authors.forename: Atsushi
authors.initials: A
authors.lastname: Urano
authors.forename: Tatsutoshi
authors.initials: T
authors.lastname: Nakahata
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Toshio
authors.initials: T
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D002450:Cell Communication / Q000502:physiology*; D018929:Cell Culture Techniques / Q000379:methods*; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D017494:Proton Pumps / Q000378:metabolism* / Q000494:pharmacology; D006180:Proton-Translocating ATPases; D017154:Stromal Cells / Q000166:cytology* / Q000378:metabolism*
chemical_list: C432920:Atp6v0a2 protein, mouse; D017494:Proton Pumps; D006180:Proton-Translocating ATPases