CCAAT/enhancer binding protein-mediated regulation of TGFβ receptor 2 expression determines the hepatoblast fate decision

Examined the function of TGFBR2 in the hepatoblast fate decision using hESC-derived HBC. hESC-derived HBCs purified and maintained (HBCs passaged more than three times) on human laminin 111 (LN111)-coated dishes were used. The HBC population was nearly homogeneous and expressed human hepatoblast markers such as alpha-fetoprotein (AFP), albumin (ALB), cytokeratin 19 (CK19) and EPCAM, and most of the colonies observed on human LN111-coated plates were ALB and CK19 double positive. The HBCs were capable of repopulating the liver of carbon tetrachloride (CCl4)-treated immunodeficient mice. This study reveals a molecular mechanism underlying the lineage commitment of human hepatoblasts (hepatocyte and biliary differentiation) controlled by a gradient of TGFβ signaling. It provides the first evidence of c/EBP-mediated regulation of TGFBR2 expression in the human hepatoblast fate decision.