Danmarks Grundforskningsfond – Centers of Excellence - ATLAS - DG Center for Functional Genomics and Tissue Plasticity

Tissue plasticity, i.e. the ability of tissues to adapt to changes in the physiological environment, is essential in health and disease. However, our understanding of responses within discrete cell types and cross-talk between these in the complex tissue setting is limited. The overarching aim of ATLAS is to gain detailed in situ insight into how metabolic stress such as high or low-caloric intake, alcohol and drugs affects the programming of specific cell types in metabolically very responsive tissues such as the liver and adipose tissues. The genome and its associated layers of epigenomic information represent a unique source of information not only for recording changes in programming but also for understanding how these occur. We will therefore take a genome-centric approach combining novel strategies for tagging specific cell types in vivo with advanced genomic tools. This will allow us to record dynamic changes in the epigenome and transcriptome of individual cell types in their natural organ context in mouse models. Moreover, by combining this approach with technologies used to target specific cell types in liver and fat tissues in vivo, we will determine the significance of the recorded changes in tissue plasticity and disease development. Finally, we will apply the knowledge obtained from mouse model systems for translational analyses of human liver and fat biopsies to improve our understanding of how changes in cell programming contributes to human physiology.