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Role of transcription factor CCAAT /enhancer‐binding protein alpha in human fetal liver cell types in vitro
Author(s) -
Gerlach Jörg C.,
Over Patrick,
Foka Hubert G.,
Turner Morris E.,
Thompson Robert L.,
Gridelli Bruno,
Schmelzer Eva
Publication year - 2015
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/hepr.12420
Subject(s) - biology , ccaat enhancer binding proteins , microbiology and biotechnology , transcription factor , liver cell , medicine , nuclear protein , gene , biochemistry
Aim The transcription factor CCAAT /enhancer‐binding protein alpha ( C / EBP α) has been shown to play an important role in liver development, cell proliferation and differentiation. It is, however, largely unknown if C / EBP α regulates cell differentiation and proliferation differently in the diverse cell types of the human liver. We investigated the role of C / EBP α 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/EBP α 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 / EBP α 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/EBP α 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 / EBP α are specific for the different human fetal liver cell types, using an advanced 3‐D perfusion bioreactor as a human in vivo ‐like model.