Fig. 2

Pluripotent stem cell (PSC) derived liver organoids. PSCs are provided with signalling cues to differentiate along the endoderm lineage into cells resembling the definitive endoderm (DE), posterior foregut (PFG) and hepatic endoderm (HE). These intermediate endoderm lineage progenitors are utilized to generate various liver organoids. The DE can use to generate the midgut (MG) and foregut (FG) spheroids. The MG and FG co-culture induces hepato-biliary-pancreatic (HBP) organogenesis at the boundary to generate the HBP organoids containing cell and structure resembling the duodenum (Duo), pancreas (Pan) and liver that are interconnected by the biliary (Bil) structure. PFG can be employed to generate multi-cellular liver organoids containing both parenchymal (hepatocytes) and non-parenchymal (HSCs and Kupffer cells) cells. The HE can be co-culture with mesenchymal stem cells and HUVEC to produce liver buds that further mature into vascularized tissues when transplanted in mice. Multiple groups have also further differentiated the HE to generate liver organoids that contain only cholangiocytes or hepatocytes, or hepatobiliary organoids containing both liver parenchymal cell types in different configurations