Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells
Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells
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DOI：
10.1016/j.bbrc.2005.11.146
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发表时间：
2006-02-03
影响因子：
3.1
通讯作者：
Kitamura, T
中科院分区：
文献类型：
--
作者：
Nakajima, H;Shibata, F;Kitamura, T
免疫抑制因子（ISF）是液泡膜ATP酶质子泵的一个亚单位。我们先前鉴定了一种短形式的ISF（ShIF）作为基质衍生因子，其支持突变Ba/F3细胞的不依赖于精氨酸的生长。在这里，我们报告了ISF/ShIF支持原代造血干细胞（HSC）的自我更新和扩增。将小鼠骨髓细胞与过表达ISF或ShIF的基质细胞系（MS 10/ISF或MS 10/ShIF）共培养，不仅能增强其集落形成活性和长期培养起始细胞的数量，而且能维持HSC的竞争性增殖活性。这种干细胞支持活性依赖于ISF/ShIF的质子转移功能。ISF/ShIF转染细胞系的基因表达分析显示，分泌的卷曲相关蛋白-1和金属蛋白酶-3的组织抑制剂的下调，并在MSIO/ISF细胞中恢复其表达部分逆转其增强的LTC-IC支持活性至正常水平。这些结果表明，ISF/ShIF通过调节Wright活性和细胞外基质来增强基质细胞对HSC的支持活性。(c)2005年爱思唯尔公司All rights reserved.
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 selfrenewal 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 metalloprotemase-3, and the restoration of their expressions in MSIO/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 Writ-activity and the extracellular matrix. (c) 2005 Elsevier Inc. All rights reserved.