Figure 10.
Generating hepatocytes and β-cells from embryonic stem cells. The top diagram schematically shows the lineage relationship between ES cells, endoderm, liver, and pancreas. The lower panel shows the relative developmental stage and time in culture (days – d).
Culturing ES cells (ESCs) in activin mimics the activity of Nodal and induces specification of a mesendodermal progenitor. Persistent culture in high activin promotes definitive endoderm (DE) formation. DE cultures exposed to hepatic inducing factors (FGF and/or BMP) form hepatoblasts, whereas pancreatic inducing factors (CYC, cyclopamine; FGF10; and RA, Retinoic acid) promote posterior foregut and pancreatic fate. Further manipulations of the culture conditions promote formation of specialized organ lineages, such as hepatocytes and pancreatic endocrine cells. Molecular markers that define each cell type are shown within the colored box.
Abbreviations: HGF, hepatocyte growth factor; Dex, dexamethazone; OSM, oncostatin M; AFP, alphafetoprotein; Tat, tyrosine amino transferase; Cyp3a11, cytochrome superfamily p450 member 3a11.