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

doi:10.1016/j.bbrc.2005.11.146

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 journal › Article › peer-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 language	English
Pages (from-to)	35-42
Number of pages	8
Journal	Biochemical and Biophysical Research Communications
Volume	340
Issue number	1
DOIs	https://doi.org/10.1016/j.bbrc.2005.11.146
Publication status	Published - 2006 Feb 3
Externally published	Yes

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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10.1016/j.bbrc.2005.11.146

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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.",

keywords = "Co-culture, HSC, Hematopoietic stem cell, ISF, Immune suppressor factor, ShIF, Stromal cell",

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

note = "Funding Information: This work was supported by grants from the Ministry of Education, Science, Sports and Culture, and the Ministry of Health and Welfare of Japan. We thank M. Ohara for language assistance. ",

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T1 - Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

AU - Nakajima, Hideaki

AU - Shibata, Fumi

AU - Fukuchi, Yumi

AU - Goto-Koshino, Yuko

AU - Ito, Miyuki

AU - Urano, Atsushi

AU - Nakahata, Tatsutoshi

AU - Aburatani, Hiroyuki

AU - Kitamura, Toshio

N1 - Funding Information: This work was supported by grants from the Ministry of Education, Science, Sports and Culture, and the Ministry of Health and Welfare of Japan. We thank M. Ohara for language assistance.

PY - 2006/2/3

Y1 - 2006/2/3

N2 - 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.

AB - 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.

KW - Co-culture

KW - HSC

KW - Hematopoietic stem cell

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KW - Immune suppressor factor

KW - ShIF

KW - Stromal cell

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

Abstract

Keywords

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