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.

Twist in hepatocellular carcinoma: pathophysiology and therapeutics

“…During the embryonic development stage, Twist plays a vital role in hepatocyte differentiation, mainly in mesoderm development, a part of EMT [13,19]. However, uncontrolled and overexpressed Twist contributes to HCC development.…”

VEGF165 expressing bone marrow mesenchymal stem cells differentiate into hepatocytes under HGF and EGF induction in vitro

“…There are many studies using HGF and EGF in the hepatocyte inducing protocol, and the concentrations of HGF and EGF showed wide ranges (Snykers et al 2009). The concentration of HGF ranges from 20 ng/ml to 150 ng/ml (Banas et al 2007;Kazemnejad et al 2008;Talens-Visconti et al 2006;Yamamoto et al 2008), and the concentration of EGF ranges from 10 ng/ml to 50 ng/ml (Kazemnejad et al 2008;Lange et al 2005;Shi et al 2005). Wang et al (2004) induced isolated BMMSCs with HGF in vitro at a concentration of 50 ng/ml, which mimicked the injured liver microenvironment.…”

Distinct Stem Cells Subpopulations Isolated from Human Adipose Tissue Exhibit Different Chondrogenic and Osteogenic Differentiation Potential

“…Therefore, most of the research work that can be found on ASCs is based on previous studies on BM-MSCs [11]. ASCs have also a great differentiation potential, demonstrated by a number of studies that have shown their neurogenic [1,12,13], cardiomyocyte and myocyte [14][15][16][17], endothelial cells [1,15], hepatocytes [18,19], adipogenic [1,20,21], and of course osteogenic and chondrogenic differentiation potential [22][23][24][25][26].…”