Multiscale, Multimodal Analysis of Skin and Spatial Cell Organization

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Project Summary/Abstract Tissue vasculature and lymphatics are an essential component of every organ and transport blood and lymph around the body, performing essential functions such as vasodilation regulation and immune cell transport. The goal of this supplemental proposal is to collaborate with the HuBMAP ZIPCODE project to develop a panel of antibodies that are specific for vascular and lymphatic cells and structures. We will provide this as a resource for the HuBMAP community for more comprehensive endothelial and lymphatic cell mapping across HuBMAP tissue mapping centers. We will generate data by staining those antibodies in skin using two multiplexed imaging technologies that are currently in use in HuBMAP (CODEX and Cell DIVE), using sequentially sectioned skin samples. We will use existing algorithms for 2D cell classification and 3D volume reconstruction of vascular and lymphatic cell types in these sequential sections. This data will be used as a resource by the HIVE and broader HuBMAP community for building maps of vascular and lymphatics vessels. Together with the ZIPCODE work, our project will help guide efforts across HuBMAP to triangulate distance between the closest artery, vein, and lymphatic capillary and relationships with nearest immune cells and other cell types. We will work with the ZIPCODE team to develop marker sets, best practices, and guidelines to enable efficient alignment and adoption across the Tissue Mapping Centers (TMCs) and activities in HuBMAP. To achieve this, we will work as a collaborative team to coordinate with the Anatomical Structures, Cell Types, plus Biomarkers (ASCT+B) tables, Organ Mapping Antibody Panels (OMAPs), data analysis working group, and HuBMAP Integration, Visualization & Engagement (HIVE) Collaboratory. We envisage that this granular mapping of endothelial cells and lymphatics will help incorporate cellular ZIP codes in spatial tissue profiling, i.e., connecting cellular function to the triangular distance between the closest artery, vein, and lymphatic capillary and provide new data on spatial location and functions of neighboring cells.