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Hepatol Res. 2015 Aug;45(8):919-32. doi: 10.1111/hepr.12420. Epub 2014 Oct 9.

Role of transcription factor CCAAT/enhancer-binding protein alpha in human fetal liver cell types in vitro.

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Department of Surgery and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
Department of Surgery, ISMETT - Mediterranean Institute for Transplantation and Advanced Specialized Therapies, Palermo, Italy.



The transcription factor CCAAT/enhancer-binding protein alpha (C/EBPα) has been shown to play an important role in liver development, cell proliferation and differentiation. It is, however, largely unknown if C/EBPα regulates cell differentiation and proliferation differently in the diverse cell types of the human liver. We investigated the role of C/EBPα in primary human fetal liver cells and liver cell subpopulations in vitro using a 3-D perfusion bioreactor as an advanced in vivo-like human organ culture model.


Human fetal liver cells were investigated in vitro. C/EBPα gene expression was knocked down using siRNA or overexpressed by plasmid transfection. Cell type-specific gene expression was studied, cell populations and their proliferation were investigated, and metabolic parameters were analyzed.


When C/EBPα gene expression was knocked down, we observed a significantly reduced expression of typical endothelial, hematopoietic and mesenchymal genes such as CD31, vWF, CD90, CD45 and α-smooth muscle actin in fetal cells. The intracellular expression of hepatic proteins and genes for liver-specific serum proteins α-fetoprotein and albumin were reduced, their protein secretion was increased. Fetal endothelial cell numbers were reduced and hepatoblast numbers were increased. C/EBPα overexpression in fetal cells resulted in increased endothelial numbers, but did not affect mesenchymal cell types or hepatoblasts.


We demonstrated that the effects of C/EBPα are specific for the different human fetal liver cell types, using an advanced 3-D perfusion bioreactor as a human in vivo-like model.


CCAAT/enhancer-binding protein alpha; bioreactor; hepatoblast; hepatocyte; liver


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