Molecular mechanisms controlling differentiation of pluripotent cells into endoderm.

During the last decade various stem cells have been derived from adult or embryonic human tissues. These cells offer new prospects to treat degenerative diseases, since they can specialise into many mature cell types that could be useful for cell based therapies. However, robust protocols allowing the production of fully functional specialised cells still need to be established. The generation of such cell types may ultimately only be achievable by recapitulating a normal path of development in vitro. But the sequential events leading to the formation of the primary germ layers, the building block of the body‘s organs, remain obscure. Thus, the understanding of the mechanisms controlling the specification of the primary germ layers has a major importance for regenerative medicine. Here, I propose to use human Embryonic Stem cells (hESCs) to study the mechanisms controlling differentiation of the endoderm germ layer, from which originate the pancreas, liver, lungs, and gut. While the objective of this project is to control differentiation of hESCs into endoderm lineages, the insight that will be gained could also be used to convert adult cells to endodermal cells by recapitulating the developmental pathway that forms this tissue during normal development.