Differentiation of mouse embryonic stem cells into growth hormone and prolactin expressing cells in vitro

Embryonic stem (ES) cells provide an excellent in vitro model system to investigate the cellular and molecular events that drive lineage-specific commitment and differentiation and have considerable potential as agents for novel cell-based therapies. While culture methods for directed in vitro differentiation of ES into neuroectodermal and mesodermal derivatives are relatively well established, little is known about the capacity of ES cells to generate the hormone secreting lineages of the pituitary. Here we show that extended culture of adherent embryoid bodies (EBs) results in the induction of pituitary-specific progenitor marker genes and pituitary hormonal markers. GH-expressing cells comprise approximately 2% of the total viable cell population and exhibit dense granular cytoplasmic immunoreactivity. These data demonstrate for the first time that cell types which have the characteristics of pituitary somatotropes and lactotropes can be generated by in vitro differentiation of mouse ES cells.