Fig. 1

Stem cell and progenitor liver organoids. Top panel: Proliferating bipotent biliary organoids isolated from patient liver tissue can be maintained in culture as an expandable cell source and differentiated into functional cholangiocytes or hepatocytes. This approach has been employed to derived tumoroids from the three major liver cancer subtypes. Middle panel: Using similar approach with additional hepatocyte supporting signaling factors, proliferating hepatocytes can also be derived from liver tissues. These proliferating hepatocytes can be further matured into highly functional hepatocytes. (Bottom panel): Transdifferentiation of fibroblast to liver organoids. Fibroblast over-expressing (OE) SV40 large T antigen (SV40LT) is transdifferentiated into human-induced hepatocyte organoids (HiHeps), using a combination of FOXA3, HNF1A and HNF4A. Introduction of various HCC oncogenes transform the HiHeps into liver cancer organoids