Surfing the wave to differentiation

Oscillating waves of DNA methylation revealed in embryonic stem cells exiting pluripotency

Graphic abstract © Steffen Rulands, MPI-PKS / CSBD


Embryonic stem cells, the early unspecified cells of the embryo, are pluripotent - they have the remarkable capacity of generating any cell type in the adult body. During this phase in development the DNA undergoes large-scale epigenetic modifications, i.e. changes that do not involve alterations in the DNA sequence. These small chemical additions are called DNA methylation. As a result of these processes the DNA in cells carries distinct molecular marks that assign their fate during later stages of development.

Steffen Rulands, research group leader at the CSBD and the MPI for the Physics of Complex Systems (MPI-PKS), and his collaborators from the Babraham Institute and the University of Cambridge have now found that these marks undergo rapid, periodic changes in cells that are exiting from pluripotency into early embryonic development. Combining single-cell sequencing and approaches from theoretical physics the researchers were able to unveil the dynamical rules that govern DNA methylation from the otherwise static information provided by these experiments. Using time-course experiments and novel techniques in genomics the researchers showed the emergence of collective oscillations in molecular DNA modifications and that these processes are synchronised throughout the genome. As a result of their work, published in Cell Systems, the researchers showed that these epigenetic oscillations are paralleled by oscillations in short-lived transcripts, the products of gene expression.

First-author of the publication, Steffen Rulands, says, “Our discovery gives fresh insight into the molecular processes underlying how stem cells are directed into becoming different cells of our body. It is possible, that the loss of cell identity, for example in cancer and other diseases, occurs through similar mechanisms as in embryonic stem cells.”

He adds, “Our publication is a result of the cross-disciplinary partnership between epigenetics researchers and physicists, which again shows the potential of accessing fundamental biological questions with theoretical physics methods. I’m very happy to be part of this multi-disciplinary environment!”

Congratulations, Steffen!

Steffen Rulands, Heather J Lee, Stephen J Clark, Christof Angermueller, Sébastien A Smallwood, Felix Krueger, Hisham Mohammed, Wendy Dean, Jennifer Nichols, Peter Rugg-Gunn, Gavin Kelsey, Oliver Stegle, Benjamin D Simons, Wolf Reik: Genome-scale oscillations in DNA methylation during exit from pluripotency. Cell Systems
DOI: 10.1016/j.cels.2018.06.012