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BPCPPDYSOE21 – wissenschaftliches Programm

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BP: Fachverband Biologische Physik

BP 3: Focus Physics of Stem Cells

BP 3.3: Vortrag

Montag, 22. März 2021, 09:40–10:00, BPc

Inference of emergent spatio-temporal processes from single-cell sequencing reveals feedback between de novo DNA methylation and chromatin condensates — •Fabrizio Olmeda1, Tim Lohoff2, Stephen Clark2, Laura Benson2, Felix Krueger2, Wolf Reik2,3, and Steffen Rulands1,41Max Planck Institute for the Physics of Complex Systems, Dresden, Germany — 2The Babraham Institute, Cambridge, UK — 3University of Cambridge, Cambridge, UK — 4Center for Systems Biology Dresden, Dresden, Germany

Recent breakthroughs in single-cell genomics allow probing molecular states of cells with unprecedented detail along the sequence of the DNA. Biological function relies, however, on emergent processes in the three-dimensional space of the nucleus, such as droplet formation through phase separation. Here, we use single-cell multi-omics sequencing to develop a theoretical framework to rigorously map epigenome profiling along the DNA sequence onto a description of the emergent spatial dynamics in the nucleus. We show how DNA methylation patterns of the embryonic genome are established through the interplay between spatially correlated DNA methylation and topological changes to the DNA. This feedback leads to the predicted formation of condensates of methylated DNA. Our work provides a general framework of how mechanistic insights into emergent processes underlying cell fate decisions can be gained by the combination of single-cell multi-omics and methods from theoretical physics.

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