Setting the epigenetic stage for differentiation: a collective phenomenon

The self-organisation of cells during embryonic development is one of the most intriguing non-equilibrium processes in nature. How do cells coordinate their behaviour in order to build a living organism? Recent technological advances, for example in genomics, for the first time allow us to probe microscopic states of these processes with unprecedented detail. But how can detailed quantitative information on the microscopic scale be translated into a mechanistic understanding of the collective degrees of freedom that determine biological function at the cellular scale? In this talk, I will give the example of epigenetic patterning in early embryonic development to demonstrate how core concepts from non-equilibrium physics can help gain understanding of the collective processes underlying cell fate regulation.

During early development, when the first cell fate decisions are made, the genome undergoes large-scale changes in epigenetic DNA modifications (DNA methylation) and chromatin structure. As a result of these processes cells carry distinct epigenetic marks that assign their fate during later stages of development and adulthood. But how are these epigenetic marks so robustly established? Combining novel methods from single-cell multi-genomics with non-equilibrium physics we find universal scaling behaviour in the processes leading to the establishment of epigenetic marks. We show that these phenomena result from long-range interactions mediated by the interplay between chemical and topological modifications of the DNA. Our work sheds new light on epigenetic mechanisms involved in cellular decision making. It also highlights how mechanistic insights into the molecular processes governing cell-fate decisions can be gained by the combination of methods from genomics and non-equilibrium physics.