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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.

Author information

1
Department of Surgery and Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
2
Department of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
3
University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
4
Department of Surgery, ISMETT - Mediterranean Institute for Transplantation and Advanced Specialized Therapies, Palermo, Italy.

Abstract

AIM:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

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

PMID:
25195540
DOI:
10.1111/hepr.12420

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