Fig. 2

Liver organoids can be derived from various cells of origin. A Generation of liver organoids from healthy liver tissues. Liver organoids can be formed from hepatocytes, cholangiocytes and Lgr5⁺ liver stem cells. The isolated cells can be placed in Matrigel as extracellular matrix and seeded into culture vessels to generate organoids. Signaling pathways which are typically modulated to enable organoid formation are listed. B Generation of liver organoids from iPSCs. Liver organoids can be generated from iPSCs, usually by a three-stage differentiation process. Firstly, iPSCs can be derived to endoderm cells by exposure to Act A and Wnt. Then, these endoderm cells progress to a hepatic fate following induction of HGF and FGF signaling. These hepatic progenitors are hepatoblast-like cells and can form hepatocyte-like cells finally. C Generation of liver organoids from fibroblasts. Fibroblasts can be induced into hiHeps by exposure to FOXA3, HNF1A and HNF4A to activate trans-differentiation. Then, liver organoids can be generated from these hiHeps. D Generation of liver cancer organoids from liver cancer tissues. Similarly, liver cancer organoids can be formed from cancer cells isolated from cancer tissues. After seeding the isolated cells into culture vessels containing appropriate matrix, cancer organoids can be generated in the certain culture medium. Act A activin A, BMP bone morphogenetic protein, EGF epidermal growth factor, FGF fibroblast growth factor, HGF hepatocyte growth factor, iPSCs induced pluripotent stem cells, TGFbi transforming growth factor beta inhibitor, TNFa tumour necrosis factor-alpha