Using mRNA display to select for inhibitors of BMP signaling

Human embryonic stem cells (hESC) are derived from the early embryo and can differentiate into the three embryonic germ layers, making them potential cell sources for regenerative medicine. Prior to the use of hESC's in patients, it is essential to understand fully the signaling pathways that maintain pluripotency and direct differentiation pathways. The bone morphogenetic protein (BMP) family of signaling molecules controls multiple biological responses during early development. Recent work has demonstrated that depending on culture conditions, BMP signaling induces the differentiation of hESC's into trophectoderm or extraembryonic tissue, and in some cases, mesendoderm, presumptive mesoderm and endoderm. However, the molecular mechanism by which BMP signaling specifies the mesendoderm or trophectoderm fate remains unknown. Using a fibronectin based protein mRNA display library, our goals are to identify novel affinity reagents targeting the BMP receptor with high affinity and specificity. These reagents will be used to further explore the role of BMP signaling in hESC biology.