Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

Hideaki Nakajima, Fumi Shibata, Yumi Fukuchi, Yuko Goto-Koshino, Miyuki Ito, Atsushi Urano, Tatsutoshi Nakahata, Hiroyuki Aburatani, Toshio Kitamura

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)35-42
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume340
Issue number1
DOIs
Publication statusPublished - 2006 Feb 3

Keywords

  • Co-culture
  • HSC
  • Hematopoietic stem cell
  • ISF
  • Immune suppressor factor
  • ShIF
  • Stromal cell

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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