{Reference Type}: Journal Article
{Title}: Role of transcription factor CCAAT/enhancer-binding protein alpha in human fetal liver cell types in vitro.
{Author}: Gerlach JC;Over P;Foka HG;Turner ME;Thompson RL;Gridelli B;Schmelzer E;
{Journal}: Hepatol Res
{Volume}: 45
{Issue}: 8
{Year}: Aug 2015
{Factor}: 4.942
{DOI}: 10.1111/hepr.12420
{Abstract}: <B>OBJECTIVE: </B>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.<BR><B>METHODS: </B>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.<BR><B>RESULTS: </B>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.<BR><B>CONCLUSIONS: </B>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.