Here, we present efficient strategies to differentiate ES cells either into pancreatic or into hepatic cell types. We recommend a strategy to select nestin+ cells, an early progenitor cell type with high developmental plasticity, followed by differentiation induction with specific growth and extracellular matrix factors into pancreatic and hepatic cell types. Cells differentiating via nestin+ cells into the pancreatic and hepatic lineage expressed tissue-specific genes. Proteins characteristic for mature endocrine pancreatic or hepatic cells were synthesized and released. Further, a histotypic "spinner" culture system was introduced to generate mature insulin- and albumin-producing cells at high efficiency.