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Quantitative Approaches to Single Cell Epigenetics: Theory and Experiments

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If you have a question about this talk, please contact Dr. Adrien Hallou.

Wolf Reik – Single cell epigenome landscape of development and ageing

Epigenetic information is relatively stable in somatic cells but is reprogrammed on a genome wide level in germ cells and early embryos. Epigenetic reprogramming appears to be conserved in mammals including humans. This reprogramming is essential for imprinting, and important for the return to naïve pluripotency including the generation of iPS cells, the erasure of epimutations, and perhaps for the control of transposons in the germ line. Following reprogramming, epigenetic marking occurs during lineage commitment in the embryo in order to ensure the stability of the differentiated state in adult tissues. Signalling and cell interactions that occur during these sensitive periods in development may have an impact on the epigenome with potentially long lasting effects. The epigenome changes in a potentially programmed fashion during the ageing process; this epigenetic ageing clock seems to be conserved in mammals. Our recent work addresses the mechanisms and consequences of global epigenetic reprogramming in the germ line, and the role of passive and active mechanisms of DNA demethylation. Using single cell multi-epigenomics techniques, we are beginning to chart the epigenetic and transcriptional dynamics and heterogeneity during the exit from pluripotency, symmetry breaking, and initial cell fate decisions leading up to gastrulation. We are also interested in the potentially programmed degradation of epigenetic information during the ageing process and how this might be coordinated across tissues and individual cells.

Steffen Rulands – De-novo DNA methylation: a collective phenomenon

During early development, the genome undergoes large-scale changes in DNA methylation and chromatin structure. As a result of these processes cells carry distinct methylation marks that are associated with their fate during later stages of development and adulthood. But how are these epigenetic marks robustly established? Combining methods from single-cell multi-genomics with non-equilibrium physics we find generic scaling behaviour and self-similarity in the processes leading to the establishment of DNA methylation marks. We show that these phenomena result from long-range interactions mediated by an interplay between chemical and topological modifications of the DNA . Our work sheds new light on collective processes underlying epigenetic modifications of the DNA . 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.

This talk is part of the Theory of Living Matter Group series.

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