Shimizu Natsumi, Noda Shinichi, Katayama Kazufumi, Ichikawa Hitoshi, Kodama Hiroaki, Miyoshi Hiroyuki
Subteam for Manipulation of Cell Fate, RIKEN BioResource Center, 3-1-1 Koyadai, Tsukuba, Ibaraki, 305-0074, Japan.
Int J Hematol. 2008 Apr;87(3):239-45. doi: 10.1007/s12185-008-0048-9. Epub 2008 Mar 4.
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.
尽管造血干细胞（HSCs）与基质细胞共培养是研究造血微环境中造血作用的有用系统，但对于通过细胞间相互作用维持造血干细胞的精确细胞和分子机制知之甚少。小鼠前脂肪基质细胞系MC3T3-G2/PA6（PA6）已被证明在体外支持造血干细胞。在本研究中，对PA6细胞和不支持造血干细胞的PA6亚克隆细胞进行了微阵列分析，以鉴定负责支持造血干细胞活性的基因。基因表达谱的比较显示，在PA6亚克隆细胞中只有144个基因下调超过两倍。在这些下调的基因中，我们选择了11个候选基因，并通过在PA6亚克隆细胞中过表达这些基因来评估其对造血干细胞功能维持的作用。一个未知基因，1110007F12Rik（也称为Tmem140），预计编码一种整合膜蛋白，它部分恢复了造血干细胞支持活性的缺陷。
