Regulatory network guiding stem cell interactions within the hematopoietic niche using single cell genomics (WP1)
Integrating data from ou in vitro model of the bone marrow niche with publicly available data, this project will reveal regulatory interactions between enhancers and their target genes that are triggered by the interaction of HSCs with different types of niche cells. Regulatory interactions will be derived from co-variation of regulatory elements (ATAC-Seq) and gene expression (RNA-Seq) across individuals. Specifically, we will investigate the effect of mesenchymal stromal cells (MSCs) and MSC-derived cell types (adipocytes and osteoblasts) on the regulatory network of HSCs. These comparisons are particularly interesting since the bone marrow niche becomes more adipocyte-dense during aging. At the same HSCs show a differentiation bias of HSCs from lymphoid to myeloid lineages upon ageing, a phenomenon that has been linked to the weakening of the adaptive immune system with old age. Integrating the regulatory network with SNPs associated with common (immune-system related) diseases, as obtained from genome-wide association studies, will reveal how the age-dependent compositional change in the bone marrow niche might contribute to disease phenotypes.