A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells
A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells
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DOI：
10.1111/j.1742-4658.2008.06287.x
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发表时间：
2008-03-01
期刊：
影响因子：
5.4
通讯作者：
Ochiya, Takahiro
中科院分区：
文献类型：
--
作者：
Yamamoto, Yusuke;Banas, Agnieszka;Ochiya, Takahiro
成体干细胞可塑性的具体特征在很大程度上是未知的。最近，我们证实了人脂肪组织间充质干细胞(AT-MSCs)的肝脏分化。为了确定与肝脏分化有关的基因，我们用几种微阵列方法检测了AT-MSC来源的肝细胞(AT-MSC-HEPA)的基因表达谱。对得到的差异表达基因集(1639个克隆)进行综合分析，以确定在AT-MSC-HEPA中表达的途径。聚类分析表明AT-MSC-HEPA与全肝的基因簇具有显著的相似性，表明AT-MSC-HEPA在基因表达上与肝脏相似。进一步分析表明，AT-MSC-HEPA中丰富的基因种类和信号通路，如互补激活和凝血级联，与肝脏特异性功能有关。值得注意的是，Twist和Snail表达的减少表明在AT-MSCs向肝细胞分化的过程中发生了间充质向上皮的转变。我们的数据显示AT-MSC-HEPA与肝脏相似，提示AT-MSCs受到环境条件的调节，AT-MSC-HEPA可能有助于肝功能的基础研究以及基于干细胞的治疗的发展。
The specific features of the plasticity of adult stem cells are largely unknown. Recently, we demonstrated the hepatic differentiation of human adipose tissue-derived mesenchymal stem cells (AT-MSCs). To identify the genes responsible for hepatic differentiation, we examined the gene expression profiles of AT-MSC-derived hepatocytes (AT-MSC-Hepa) using several microarray methods. The resulting sets of differentially expressed genes (1639 clones) were comprehensively analyzed to identify the pathways expressed in AT-MSC-Hepa. Clustering analysis revealed a striking similarity of gene clusters between AT-MSC-Hepa and the whole liver, indicating that AT-MSC-Hepa were similar to liver with regard to gene expression. Further analysis showed that enriched categories of genes and signaling pathways such as complementary activation and the blood clotting cascade in the AT-MSC-Hepa were relevant to liver-specific functions. Notably, decreases in Twist and Snail expression indicated that mesenchymal-to-epithelial transition occurred in the differentiation of AT-MSCs into hepatocytes. Our data show a similarity between AT-MSC-Hepa and the liver, suggesting that AT-MSCs are modulated by their environmental conditions, and that AT-MSC-Hepa may be useful in basic studies of liver function as well as in the development of stem cell-based therapy.