Differentiation of embryonic stem cells into anterior definitive endoderm.

Anterior definitive endoderm (ADE) is both an important embryonic signaling center and a unique multipotent precursor of liver, pancreas, and other visceral organs. Here we describe a method for the differentiation of mouse embryonic stem (ES) cells to endoderm with pronounced anterior character. ADE-containing cultures can be produced in vitro by suspension (aggregation or embryoid body) culture and in a serum-free adherent monolayer culture. Purified ES cell-derived ADE cells appear committed to endodermal fates and can undergo further differentiation in vitro towards liver and pancreas with enhanced efficiency.