EpiSyStem · Epigenetics and System Biology of Stem cells and Reprogramming

Epigenetics and System Biology of Stem cells and Reprogramming

In eukaryotic cells, DNA is tightly packaged as chromatin in a form of nucleosomes, comprised of 147 bp of DNA wrapped around two copies each of the core histones H2A, H2B, H3 and H4. Nucleosomes are separated by linker DNA, bound by a linker histone, H1. Chromatin structure is controlled by protein complexes generally called chromatin modifiers, which affect DNA accessibility, DNA-protein interactions and chromatin organisation. Chromatin structure, regulation and plasticity dictate many of the nuclear processes, e.g. replication, transcription, cell cycle, protein dynamics and more - all of which ultimately facilitate or repress changes in transcription, either locally or globally. Chromatin is the basic regulatory unit of life and as such, it controls the developmental and functional states of all cells, including pluripotency. The aim of EpiSyStem was to concentrate on technological advances and state-of-the-art methods which enable a fresh and unbiased look at some of the long-standing questions in epigenetics. We combined chromatin biology in stem cells, early embryos and reprogramming (including the modelling of human neurological, chromatin-related, diseases) with bioinformatics, epigenetics/epigenomics, and systems biology at the population and the single-cell/single embryo level. This multidisciplinary approach enabled profound training with a deep, systems-level understanding of chromatin biology and epigenetic regulation of stem cells and reprogramming: 1. Histone dynamics and development of novel single-cell technologies: histone turnover in cell populations and single cells, to understand the consequences of cell-to-cell variability in the epigenome on phenotypic heterogeneity. 2. Identify the components and mechanisms that control chromatin regulation in early development: chromatin plasticity and epigenetic decisions in early mouse embryos, in embryonic stem cells using SNAP-tag technology, in later developmental stages during neurogenesis and neuronal/glial fate decisions, and, using specific chromatin-related antibodies and reagents. 3. Comprehensive mapping of chromatin structure and function during differentiation: multi-disciplinary state-of-the-art approaches in stem cell differentiation, including mass-spectrometry, CRISPR genome editing and live-cell imaging of endogenously tagged genomic loci, and single-cell transcriptomics and epigenomic technologies. 4. Study and understand chromatin regulation in selected disease models of iPSCs: induced pluripotent stem cell (iPSC) models of chromatin-related diseases caused by symmetric dosage imbalances in epigenetic regulators.

Data: CORDIS, © European Union