A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells

Yusuke Yamamoto, Agnieszka Banas, Shigenori Murata, Madoka Ishikawa, Chun R. Lim, Takumi Teratani, Izuho Hatada, Kenichi Matsubara, Takashi Kato, Takahiro Ochiya

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64 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1260-1273
Number of pages14
JournalFEBS Journal
Volume275
Issue number6
DOIs
Publication statusPublished - 2008 Mar 1

Keywords

  • Adipose tissue
  • Gene ontology
  • Hepatocyte differentiation
  • Mesenchymal stem cell
  • Microarray

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Yamamoto, Y., Banas, A., Murata, S., Ishikawa, M., Lim, C. R., Teratani, T., Hatada, I., Matsubara, K., Kato, T., & Ochiya, T. (2008). A comparative analysis of the transcriptome and signal pathways in hepatic differentiation of human adipose mesenchymal stem cells. FEBS Journal, 275(6), 1260-1273. https://doi.org/10.1111/j.1742-4658.2008.06287.x