Pluripotent stem cells and early embryonic development

Understanding the epigenetic dynamics during early embryonic development

The genomic blueprint of the eukaryote is stored into structures referred to as chromatin, in which DNA is tightly packed with the help of histone proteins. Through various histone post-translation modifications (hPTMs), the chromatin architecture could be modified to ensure proper dynamic control of gene transcription. Currently, the best-studied hPTMs are acetylation, methylation, and phosphorylation. It has been suggested that these hPTMs form ‘histone codes’, enabling chromatin dynamics modulation. Here, we are interested in the dynamic regulation of the epigenome during early embryonic development, particularly on hPTMs. Our work utilizes human and mouse pluripotent stem cells (PSCs) to dissect the basic molecular mechanism, including the role of these hPTMs in early embryonic development. To better understand these processes, we are using a multi-omics approach, which includes techniques such as Cut&Tag, RNA-seq, ATAC-seq and Bisulfite-seq on single-cell and bulk levels.

Interplay between metabolism and epigenetics during early embryonic development

Metabolic pathways are emerging as a key regulatory mechanism to control cellular function, potential, and state through the dynamic regulation of the epigenome. In particular, embryonic development is characterised by significant metabolic, epigenetic, and cellular changes associated with different developmental stages, suggesting that metabolism may play a key role in regulating cell fate decisions. But until now, the precise molecular interplay between metabolism and the epigenome remains poorly understood. Our main goal is to understand the mechanisms that link metabolism with epigenetic changes and cellular potential, focusing on pluripotent stem cells and early embryonic development. We are building a comprehensive dataset of metabolic states in human and mouse stem cells and are assessing the impact of induced metabolic changes on PSC potential, histone and DNA methylation, and the relevant epigenetic enzymes. Elucidating these mechanisms will reveal molecular principles involved in the regulation of the epigenome and affecting PSC potential and state. This knowledge will form the basis for novel PSC differentiation strategies for regenerative medicine and will also contribute to our understanding of metabolic disease states and ageing.