Identification of genes potentially involved in supporting hematopoietic stem cell activity of stromal cell line MC3T3-G2/PA6.

Identification of genes potentially involved in supporting hematopoietic stem cell activity of stromal cell line MC3T3-G2/PA6.
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DOI:
10.1007/s12185-008-0048-9
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发表时间:
2008-04
影响因子:
2.1
通讯作者:
Miyoshi H
Miyoshi H
中科院分区:
医学4区
文献类型:
--
作者:
Shimizu N;Noda S;Katayama K;Ichikawa H;Kodama H;Miyoshi H

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虽然造血干细胞(HSCs)与基质细胞的共培养是一个有用的系统,研究造血在生态位,鲜为人知的是,关于精确的细胞和分子机制,维持HSCs通过细胞-细胞相互作用。小鼠前脂肪基质细胞系MC 3 T3-G2/PA 6(PA 6)已被证明在体外支持HSC。在这项研究中,对PA 6细胞和HSC非支持的PA 6亚克隆细胞进行微阵列分析,以确定负责支持HSC活性的基因。基因表达谱比较显示,PA 6亚克隆细胞中只有144个基因下调了两倍以上。在这些下调的基因中,我们选择了11个候选基因,并通过在PA 6亚克隆细胞中过表达这些基因来评估HSC功能的维持。一个未知的基因,1110007 F12 Rik(也被命名为Tmem 140),这是预测编码一个完整的膜蛋白,证明了部分恢复的缺陷,HSC支持活动。本文的在线版本(doi:10.1007/s12185-008-0048-9)包含补充材料,可供授权用户使用。
Although coculture of hematopoietic stem cells (HSCs) with stromal cells is a useful system to study hematopoiesis in the niche, little is known regarding the precise cellular and molecular mechanisms of maintaining HSCs through cell–cell interactions. The murine preadipose stromal cell line MC3T3-G2/PA6 (PA6) has been demonstrated to support HSCs in vitro. In this study, microarray analysis was performed on PA6 cells and HSC-nonsupporting PA6 subclone cells to identify genes responsible for supporting HSC activity. Comparison of gene expression profiles revealed that only 144 genes were down-regulated by more than twofold in PA6 subclone cells. Of these down-regulated genes, we selected 11 candidate genes and evaluated for the maintenance of HSC function by overexpressing these genes in PA6 subclone cells. One unknown gene, 1110007F12Rik (also named as Tmem140), which is predicted to encode an integral membrane protein, demonstrated a partial restoration of the defect in HSC-supporting activity. The online version of this article (doi:10.1007/s12185-008-0048-9) contains supplementary material, which is available to authorized users.
DOI: 10.1084/jem.176.2.351
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