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首页> 外文期刊>Cell and Tissue Research >Study of transforming growth factor alpha for the maintenance of human embryonic stem cells.
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Study of transforming growth factor alpha for the maintenance of human embryonic stem cells.

机译：用于维持人类胚胎干细胞的转化生长因子α的研究。

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Human embryonic stem cells (hESCs) have great potential for regenerative medicine as they have self-regenerative and pluripotent properties. Feeder cells or their conditioned medium are required for the maintenance of hESC in the undifferentiated state. Feeder cells have been postulated to produce growth factors and extracellular molecules for maintaining hESC in culture. The present study has aimed at identifying these molecules. The gene expression of supportive feeder cells, namely human foreskin fibroblast (hFF-1) and non-supportive human lung fibroblast (WI-38) was analyzed by microarray and 445 genes were found to be differentially expressed. Gene ontology analysis showed that 20.9% and 15.5% of the products of these genes belonged to the extracellular region and regulation of transcription activity, respectively. After validation of selected differentially expressed genes in both human and mouse feeder cells, transforming growth factor α (TGFα) was chosen for functional study. The results demonstrated that knockdown or protein neutralization of TGFα in hFF-1 led to increased expression of early differentiation markers and lower attachment rates of hESC. More importantly, TGFα maintained pluripotent gene expression levels, attachment rates and pluripotency by the in vitro differentiation of H9 under non-supportive conditions. TGFα treatment activated the p44/42 MAPK pathway but not the PI3K/Akt pathway. In addition, TGFα treatment increased the expression of pluripotent markers, NANOG and SSEA-3 but had no effects on the proliferation of hESCs. This study of the functional role of TGFα provides insights for the development of clinical grade hESCs for therapeutic applications.
机译：人类胚胎干细胞（hESCs）具有自我再生和多能性，因此在再生医学方面具有巨大潜力。饲养细胞或其条件培养基是维持hESC处于未分化状态所必需的。假定饲养细胞会产生生长因子和细胞外分子，以维持hESC在培养中。本研究旨在鉴定这些分子。通过微阵列分析了支持性饲养细胞，即人包皮成纤维细胞（hFF-1）和非支持性人肺成纤维细胞（WI-38）的基因表达，发现445个基因被差异表达。基因本体分析表明，这些基因的产物的20.9％和15.5％分别属于细胞外区域和转录活性的调控。在人和小鼠饲养细胞中验证了选定的差异表达基因后，选择了转化生长因子α（TGFα）进行功能研究。结果表明，hFF-1中TGFα的敲低或蛋白中和导致早期分化标志物的表达增加和hESC的附着率降低。更重要的是，TGFα通过在非支持条件下体外分化H9来维持多能基因表达水平，附着率和多能性。 TGFα处理激活了p44 / 42 MAPK途径，但没有激活PI3K / Akt途径。另外，TGFα处理增加了多能标记，NANOG和SSEA-3的表达，但对hESC的增殖没有影响。 TGFα功能作用的这项研究为开发用于治疗应用的临床级hESC提供了见识。

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