Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells.
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.
Nakajima
Hideaki
H
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
Shibata
Fumi
F
Fukuchi
Yumi
Y
Goto-Koshino
Yuko
Y
Ito
Miyuki
M
Urano
Atsushi
A
Nakahata
Tatsutoshi
T
Aburatani
Hiroyuki
H
Kitamura
Toshio
T
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*
C432920:Atp6v0a2 protein, mouse; D017494:Proton Pumps; D006180:Proton-Translocating ATPases