PROJECT SUMMARY – HEART OSP The human heart is vital for our survival and health, and it presents remarkable anatomical, cellular and functional heterogeneity. The four chambers of the heart, together with specialized arteries, veins, valves and conduction cells, perform distinct yet essential physiological functions. A significant gap of knowledge is that different cell’s molecular signature, spatial distribution and interactions, and functional state remain little understood at the single-cell level. The goal of the heart Organ-Specific Project (OSP) is to address this knowledge gap and generate high quality, single-cell resolution, longitudinal imaging and multiomics data of normal human hearts across the entire human lifespan. To achieve this goal, we will generate: 1) Human heart atlases. Spatially resolved atlases will provide a highly user friendly, publicly available, searchable database of the most comprehensive multi-omic, single cell analysis of the normal human hearts. Molecular data will be richly annotated with additional clinical and demographic data. 2) Computational methods. In addition to the atlas data, the critical computational tools and pipelines developed in this project will be available to the research community. These include methods and pipelines for processing multi-omics and imaging data, inference of cell- specific regulatory and signaling pathways, correlation of mesoscale imaging and molecular imaging features, as well as database algorithms for the query, exploration and visualization of highly complex data. 3) Access to biospecimens for follow-up studies. Biospecimens collected in this project will be banked and made available to the biomedical research community. These include freshly frozen and fixed specimens and tissue sections. In summary, the heart OSP will broadly impact the entire research community and jumpstart basic-science and medical discoveries based on a sophisticated understanding of the key molecular circuits underlying the development and aging of human heart.