IMR Press / FBL / Volume 12 / Issue 5 / DOI: 10.2741/2181

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on as a courtesy and upon agreement with Frontiers in Bioscience.

Hepatic differentiation and transcriptional profile of the mouse liver epithelial progenitor cells (LEPCs) under the induction of sodium butyrate
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1 Department of Cell Biology, Second Military Medical University, Xiangyin Rd. 800, Shanghai 200433, P, R, China
2 State Key Laboratory of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai 200433, P. R. China
3 Key Laboratory of Stem Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road Shanghai 200031, P. R. China
4 The Stem Cell Institute, Department of Laboratory Medicine and Pathology, University of Minnesota, 2001 6th street SE, Minneapolis, MN 55455, USA
Front. Biosci. (Landmark Ed) 2007, 12(5), 1691–1698;
Published: 1 January 2007

The liver regenerates by progenitor cells when it is damaged in chronic liver diseases and extensive damage. The progenitor cells, also termed "oval cells" according to their morphological traits, can differentiate into hepatocytes and bile duct cells in vivo. To better understand the transcriptional pattern that accompanies the hepatic differentiation of oval cells, we applied cDNA microarray to analyze the oval cell-derived liver epithelial progenitor cells (LEPCs) during in vitro induced differentiation. Upon exposure to sodium butyrate, a histone deacetylase inhibitor, cultured LEPCs differentiate and express functional hepatocyte markers albumin, tryptophan 2, 3-dioxygenase and alcohol dehydrogenase. For expression profiling, cells were harvested at 6 h, 12 h, 1 d, 3 d and 7 d after exposure to sodium butyrate. After analyzing the microarray data by SOM clustering, total of 796 differentially regulated genes were grouped into 48 clusters. Consistent with the phenotype change of LEPCs after sodium butyrate treatment, many hepatocyte functional genes are revealed by analyzing the clusters containing genes up-regulated through all the time points. The clusters, containing down-regulated genes immediately after the induction, are also analyzed. The microarray data was validated by analyzing the expression of selected genes by quantitative real-time PCR. A set of genes expressed synergistically in these clusters may play a central role during the process of differentiation. Sodium butyrate decreases cyclin B1 and Cdk4 expression, which would be associated with LEPCs growth arrest shortly after treatment. Bmi1, a polycomb group protein, is also down-regulated immediately after treatment and remains at a low level during the induction. These findings highlight the key molecular mechanisms by which sodium butyrate, mediates its effects on cell growth arrest and induction of differentiation. In conclusion, our data reflect a global view of gene expression during hepatic differentiation of LEPCs induced by sodium butyrate.

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