Spatiotemporal analysis of mammalian embryonic development at single-cell level

Mammalian early embryonic development requires exquisite spatiotemporal gene regulation at the level of individual cells.

However, it is still unclear and remains a fundamental challenge how cell behaviours govern gastrulation and organogenesis in early embryos.

Two techniques have recently been developed to investigate cell fate decisions in early mammalian development (spatial transcriptomics at single-cell level) or to study the dynamic transition from single cells to fully formed organisms (in toto imaging), and if only these two techniques could be combined would we be able to link cell motion with cell state and more completely understand developmental processes.

There is precedence for combining live cell imaging with gene expression data in ascidians and annelids, but this has yet to be done, at scale, in more complex mammalian systems.

To this end, the proposal aims to investigate early mammalian development by linking spatial transcriptomics and in toto imaging data.

This will be the first combination of real-time tracking of cellular dynamics and spatiotemporal gene expression profiles across the developing embryo, thus providing insight into how cells move, interact with each other and how they regulate their own gene expression, ultimately revealing the fate that cells adopt.

Accordingly, I will develop a novel integration framework and generate the first cellular-resolution mammalian embryo developmental gene expression map in four dimensions that reflects both cellular dynamics and spatiotemporal gene expression profiles at the single-cell level.

Moreover, this work will pave the way for multi-omics integration, which has been increasingly explored but to date is confined to the single-cell space.