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

Authors

• Jörg C Gerlach
• Patrick Over
• Hubert G Foka
• Morris E Turner
• Robert L Thompson
• Bruno Gridelli
• Eva Schmelzer

Publication/Presentation Date

8-1-2015

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.

Volume

45

Issue

8

First Page

919

Last Page

932

ISSN

1386-6346

Published In/Presented At

Gerlach, J. C., Over, P., Foka, H. G., Turner, M. E., Thompson, R. L., Gridelli, B., & Schmelzer, E. (2015). Role of transcription factor CCAAT/enhancer-binding protein alpha in human fetal liver cell types in vitro. Hepatology research : the official journal of the Japan Society of Hepatology, 45(8), 919–932. https://doi.org/10.1111/hepr.12420

Disciplines

Medicine and Health Sciences

PubMedID

25195540

Department(s)

Department of Obstetrics and Gynecology

Document Type

Article