HNF-4α determines hepatic differentiation of human mesenchymal stem cells from bone marrow.
OBJECTIVE
To investigate the differentiation status and key factors to facilitate hepatic differentiation of human bone-marrow-derived mesenchymal stem cells (MSCs).


METHODS
Human MSCs derived from bone marrow were induced into hepatocyte-like cells following a previously published protocol. The differentiation status of the hepatocyte-like cells was compared with various human hepatoma cell lines. Overexpression of hepatocyte nuclear factor (HNF)-4α was mediated by adenovirus infection of these hepatocyte-like cells. The expression of interesting genes was then examined by either reverse transcription-polymerase chain reaction (RT-PCR) or real-time RT-PCR methods.


RESULTS
Our results demonstrated that the differentiation status of hepatocyte-like cells induced from human MSCs was relatively similar to poorly differentiated human hepatoma cell lines. Interestingly, the HNF-4 isoform in induced MSCs and poorly differentiated human hepatoma cell lines was identified as HNF-4γ instead of HNF-4α. Overexpression of HNF-4α in induced MSCs significantly enhanced the expression level of hepatic-specific genes, liver-enriched transcription factors, and cytochrome P450 (P450) genes.


CONCLUSIONS
Overexpression of HNF-4α improves the hepatic differentiation of human MSCs from bone marrow and is a simple way of providing better cell sources for clinical applications.
Chen
Mong-Liang
ML
Division of Molecular and Genomic Medicine, National Health Research Institutes, Miaoli 350, Taiwan.
Lee
Kuan-Der
KD
Huang
Huei-Chun
HC
Tsai
Yue-Lin
YL
Wu
Yi-Chieh
YC
Kuo
Tzer-Min
TM
Hu
Cheng-Po
CP
Chang
Chungming
C
D001854:Bone Marrow Cells / Q000166:cytology*; D006528:Carcinoma, Hepatocellular / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000502:physiology; D051557:Hepatocyte Nuclear Factor 4 / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology*
C496592:HNF4A protein, human; D051557:Hepatocyte Nuclear Factor 4