Open or closed: Investigating the transcriptome and epigenome of embryonic hematopoiesis at single cell resolution

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Hematopoiesis is a dynamic process by which all blood cells are generated during the lifetime of an organism. Blood cells are closely regulated by changes in the transcriptome and epigenome. Understanding how blood cells form is of fundamental importance and clinically relevant for the progress of cell replacement therapies and transplantation protocols in blood and vascular genetic- and age-related diseases. While the major anatomical sites of hematopoiesis change during a lifetime, the developmental origin of these cells remain not fully determined. Furthermore, the gene regulatory networks involved in early specification of these cells is also unresolved. Using the avian (chicken) embryo as a model organism, we propose to comprehensively define the hematopoietic genetic programming, concentrating on the early stages of embryonic development. Single-cell RNA-sequencing will be used to determine the key genes and single-cell ATAC-sequencing to identify non-coding regulatory elements followed by detailed bioinformatic analyses. We will validate key gene networks with in vivo experimentation using genome-editing tools (such as CRISPR) and advanced live microscopy. Many of the molecular processes involved in cellular reprogramming are conserved during evolution and is likely that at least some of the discoveries made in the avian model will have direct relevance to humans.