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Ontogenesis – how a fertilised egg (zygote) generates a complex multicellular organism - is a challenging, yet extremely robust phenomenon. This combination raises a hypothesis that principles of cell differentiation evolved over a million years are paradoxically simple. Also, they must be universal, e.g., independent from the organism, cell type, or stage of differentiation. Based on our previous research that coined the chrono-epigenetics theory, we infer molecular oscillations as one of the fundamental developmental/cell differentiation drivers. In this project, cyclical changes in epigenetic modifications will be sought en route from stem cell to terminal lineage fate. As a research object, murine embryonic stem cells and human-induced pluripotent stem cells will be used. Comprehensive DNA modification profiling (e.g., cytosine methylation and hydroxymethylation) will be performed at various stages of cell differentiation in addition to the analysis of chromatin architecture and transcriptome dynamics. Differentiation trajectories will be assessed based on the cyclic dynamics of epigenomic modifications and parameters of periodicity, such as oscillation amplitude, phase, and period duration. Results are expected not only to contribute to the understanding of development but also to reveal new connections with the two other fundamental biomedical issues – ageing and disease etiopathogenesis.

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