title: A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells.
abstract: 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.
authors.affiliation: Section for Studies on Metastasis, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Banas
authors.forename: Shigenori
authors.initials: S
authors.lastname: Murata
authors.forename: Madoka
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Chun R
authors.initials: CR
authors.lastname: Lim
authors.forename: Takumi
authors.initials: T
authors.lastname: Teratani
authors.forename: Izuho
authors.initials: I
authors.lastname: Hatada
authors.forename: Kenichi
authors.initials: K
authors.lastname: Matsubara
authors.forename: Takashi
authors.initials: T
authors.lastname: Kato
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ochiya
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D053687:Adult Stem Cells / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction