"The goals of regenerative medicine require a deep understanding of cell lineage and differentiation, developmental potential and fate. Stem cells representing each of the three first cell lineages of the mammalian blastocyst embryo, TS (trophectoderm), XEN (extraembryonic endoderm, exEn) and ES (epiblast) can be isolated, maintained and differentiated and provide tremendous tools for cell-based therapies.In this proposal, I will dissect the molecular mechanisms of maintenance and differentiation of XEN stem cells. The rationale is that exEn is a critical tissue for embryo survival and patterning. It also plays a role in hematopoiesis, germ cell specification and has been recently found in the endoderm of the fetus. Therefore, understanding XEN cell biology will provide important informations concerning the conditions necessary to expand and manipulate stem cells in vitro. As a consequence, this will have significant impact on the manipulation of embryonic-derived stem cells in regenerative medicine.My project will be centered around three aspects of exEn biology. What are the role(s) of the receptor tyrosine kinases (RTKs) in exEn formation? What functions exerts Wnt signaling pathway in XEN stem cell maintenance and differentiation? What are the key factors involved in their maintenance and differentiation ? This project will be achieved by combining genetic and pharmacological strategies both in vivo and ex vivo."