Induced Pluripotent Stem Cell Derived Liver Model for the Study of PNPLA3 Associated Non-Alcoholic Fatty Liver Disease

In order to identify molecular mechanisms associated with PNPLA3 associated non-alcoholic fatty liver disease, we ran RNA sequencing on human induced pluripotent stem cell-derived hepatocyte like cells that were homozygous for the wild type PNPLA3 allele, homozygous for the risk PNPLA3 allele (I148M), or had a complete knock-out of the PNPLA3 gene. The cells were then treated with either oleic acid or palmitic acid to induce a steatotic or a lipotoxic phenotype, respectively. The cells were treated with control medium or medium supplemented with 0.25 mM oleic acid or palmitic acid for 24 hours before samples were collected for RNA sequencing. Overall design: mRNA profiles of hepatocyte like cells of 3 PNPLA3 genotypes (WT, I148M, and KO) treated with 3 lipid treatments (Control, OA, and PA).