RT Journal Article
SR Electronic
T1 Induction of differentiation and metabolic reprogramming in human hepatoma cells by adult human serum
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 180968
DO 10.1101/180968
A1 Rineke Steenbergen
A1 Martin Oti
A1 Rob ter Horst
A1 Wilson Tat
A1 Chris Neufeldt
A1 Alexandr Belovodskiy
A1 Tiing Tiing Chua
A1 Woo Jung Cho
A1 Michael Joyce
A1 Bas E. Dutilh
A1 D. Lorne Tyrrell
YR 2017
UL http://biorxiv.org/content/early/2017/08/25/180968.abstract
AB Tissue culture medium routinely contains fetal bovine serum (FBS). Here we show that culturing human hepatoma cells in their native, adult serum (human serum, HS) results in the restoration of key morphological and metabolic features of normal liver cells. When moved to HS, these cells show differential transcription of 22-32% of the genes, stop proliferating, and assume a hepatocyte-like morphology. Metabolic analysis shows that the Warburg-like metabolic profile, typical for FBS-cultured cells, is replaced by a diverse metabolic profile consistent with in vivo hepatocytes. We demonstrate the formation of large lipid and glycogen stores, increased glycogenesis, increased β-oxidation, increased ketogenesis, and decreased glycolysis. Finally, organ-specific functions are restored, including xenobiotics degradation and secretion of bile, very low density lipoprotein, and albumin. Thus, organ-specific functions are not necessarily lost in cell cultures, but might be merely suppressed in FBS. Together, we showed that cells that are representative of normal physiology can be produced from cancer cells simply by replacing FBS by HS in culture media. The effect of serum is often overseen in cell culture and we provide a detailed study in the changes that occur, provide insight in some of the serum components that may play a role in the establishment of the different phenotypes, and discuss how these finding might be beneficial to a variety of research fields.