Application of Single Cell Technologies to the Study of Hematopoiesis

The Gottgens group uses a combination of experimental and computational approaches to study how transcription factor networks control the function of blood stem cells and how mutations that perturb such networks cause diseases. The group's current research focuses on (i) single cell genomics of early blood development, (ii) computer models of the transcriptional landscape of blood stem cell differentiation, (iii) transcriptional consequences of leukaemogenic mutations, and (iv) molecular characterization of human blood stem cell populations used in cell and gene therapy protocols. As requested by the session chair, this year's presentation will first provide an overview of single cell technologies, and how they are advancing our understanding of multiple facets of haematology research. This will include single cell molecular profiling, as well as single cell functional assays, and in particular also how a combination of the two allows a more precise definition of haematopoietic stem and progenitor cell types. The rest of the presentation will focus on our multidisciplinary work combining single cell molecular profiling, bioinformatics analysis and experimental/functional validation to study the normal haematopoiesis, and contrast this with 6 mouse models of pre-leukaemic disease. Comprehensive bioinformatics analysis reveals not only qualitative changes in cellular abundance, but also pinpoints the underlying molecular changes that are most likely driving the early stages of malignant disease. An overarching theme will be how single cell landscapes allow us to move seamlessly between different scales of biological investigation, from the molecular to the cellular and whole tissue scale. Finally, extrapolation to human patient data demonstrates disease relevance of gene sets identified from comparative analysis of single cell transcriptional landscapes in mouse models.