EuroSyStem brings together elite European research teams to create a unique and world-leading programme in fundamental stem cell biology. By interconnecting complementary biological and computational expertise we will drive the generation of new knowledge on the characteristics of normal and abnormal stem cells. We will pave the way for application of systems methodology by measuring and modelling stem cell properties and behaviour. Information will be mined from studies in model organisms, but our primary focus is on the paradigmatic mammalian stem cells – haematopoietic, epithelial, neural and embryonic. We will compare cellular hierarchy, signalling, epigenetics, dysregulation, and plasticity. Niche dependence, asymmetric division, transcriptional circuitry and the decision between self-renewal and commitment are linked in a cross-cutting work package. A multidisciplinary approach combines transgenesis, real time imaging, multi-parameter flow cytometry, transcriptomics, RNA interference, proteomics and single cell methodologies. SMEs will contribute to the development of enhanced resolution quantitative technologies. A platform work package will provide new computational tools and database resources, enabling implementation of novel analytical and modelling approaches. EuroSyStem will engage with and provide a focal point for the European stem cell research community. The targeted collaborations within the EuroSyStem research project will be augmented by federating European research excellence in different tissues and organisms. We will organise annual symposia, training workshops, summer schools, networking and research opportunities to promote a flourishing basic stem cell research community. This network will foster interaction and synergy, accelerating progress to a deeper and more comprehensive understanding of stem cell properties. In parallel EuroSyStem will develop WEB resources, educational and outreach materials for scientists and the lay community.