Molecular characterisation of the establishment of and exit from pluripotency in the mouse embryo by combining live-imaging and single-cell RNA-seq

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Understanding of the molecular mechanism underlying formation and differentiation of the pluripotent inner cell mass (ICM) cells in the mammalian blastocyst is essential for stem cell biology and translational medicine. Our recent studies in the mouse embryo revealed unexpected complexities in this process due to dynamic cell rearrangement and stochastic cell-to-cell heterogeneity in gene expression. Thus the mechanistic understanding requires quantitative characterisation of cell behaviour and global gene expression dynamics at a single-cell resolution. This project aims at mapping the molecular profile during specification and differentiation of the pluripotent cells in vivo using mouse embryos. We will combine the leading expertise of the two labs; live-imaging analysis of fluorescence lineage-reporter embryos in the Hiiragi lab and single-cell RNA-seq of early mammalian embryos in the Tang lab. This joint work will allow the team to characterise the full transcriptome of the single cells for which developmental history and outcome is available, thus providing the unique opportunity to study early mouse development and stem cell biology at an unprecedented level. We will particularly focus on the cell-to-cell expression heterogeneity of the ICM marker genes at a single-base resolution and address its dynamics, correlations and potential role in the establishment of and exit from pluripotency. Together this study will form the basis for understanding the molecular and cellular mechanisms of stem cell formation, maintenance and lineage-specific differentiation.