MODELLING LIVER DISEASE WITH 3D HEPATIC ORGANOIDS

Abstract

In this project, we aimed to derive a multicellular hepatic organoid containing both hepatocytes and cholangiocytes for means of modelling liver diseases. To do so, we generated a step-wise differentiation protocol for differentiating hESC, using 2D and 3D matrices in a chemically defined system, to arrive at a TBX3 expressing progenitor capable of self-organization and differentiation into hepatocytes and cholangiocytes. These cells exhibit functional properties of the liver such as albumin and APOB secretion, CYP3A4 activity, lipid accumulation, and presence of bile canaliculi. With this system, we were able to combine gene editing and global transcriptomic analysis to model and dissect the role of TM6SF2 in non-alcoholic liver disease.