Molecular mechanism of natural pluripotency establishment in the early mouse embryo based on single-cell gene expression profile

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Understanding of the molecular mechanism leading to establishment of natural pluripotency in vivo is crucial for the efficient application of stem cell biology to regenerative medicine. The principal aim of this project is to understand the molecular program underlying formation of the pluripotent inner cell mass in the mouse blastocyst, which will also elucidate molecular properties of embryonic stem cells. This project focuses on applying single-cell gene expression profiling to the mouse pre-implantation embryo, in order to comprehensively characterize molecular signature leading to the pluripotent lineage segregation. In the last two years, we have successfully established the methodologies and characterized molecular signatures within the inner cell mass cells. This led us to i) identify the molecular signature characteristic to two distinct populations in the inner cell mass, epiblast and primitive endoderm; ii) identify the earliest possible markers, thus potential key players, for the lineage segregation; iii) characterize stochastic gene expression prominent in the early developmental stages. In this proposal, we will apply the same successful strategy to characterize the segregation between the inner cell mass and trophectoderm cell lineages, likely taking place in the earlier developmental stage, morula. Altogether this will allow comprehensive characterization of key molecules and the underlying mechanism leading to the formation of ground state naive pluripotency in vivo.