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

Takayama K., Kawabata K., Nagamoto Y., Inamura M., Ohashi K., Okuno H., Yamaguchi T., Tashiro K., Sakurai F., Hayakawa T., Okano T., Furue M.K., and Mizuguchi H. Development, 2014

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.