The potential formation of teratoma/teratocarcinoma from pluripotent stem cells represents one the main obstacles to safe use stem cell-based regenerative therapy. The gene network that regulates the stem cell tumoreginicity is still largely unknown. In this study we use as model the chordate Botryllus schlosseri (Ascidiacea), wherein through a process known as vascular budding, an adult is regenerated from pluripotent cells in a sequence of morphologically abnormal developmental stages which pass through a teratoma structure. The teratoma maintains a population of cells that preserve their pluripotency and eventually re-gain positional identity and differentiate “correctly” into a functional body. In this proposed project we take advantage of this in vivo phenomenon to explore the molecular bases regulating the equilibrium between pluripotency and tumorigenicity. We propose two complementary approaches: (1) To undertake unbiased high-throughout gene screening in order to define the trascriptome implicated in the vascular budding (2) to target candidate genes involved in endomesoderm specification and characterize their spatio-temporal patterns of expression and test their functions.
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