Abstract
Several ongoing international efforts are developing methods of localizing single cells within organs or mapping the entire human body at the single cell level, including the Chan Zuckerberg Initiative's Human Cell Atlas (HCA), and the Knut and Allice Wallenberg Foundation's Human Protein Atlas (HPA), and the National Institutes of Health's Human BioMolecular Atlas Program (HuBMAP). Their goals are to understand cell specialization, interactions, spatial organization in their natural context, and ultimately the function of every cell within the body. In the same way that the Human Genome Project had to assemble sequence data from different people to construct a complete sequence, multiple centers around the world are collecting tissue specimens from diverse populations that vary in age, race, sex, and body size. A challenge will be combining these heterogeneous tissue samples into a 3D reference map that will enable multiscale, multidimensional Google Maps-like exploration of the human body. Key to making alignment of tissue samples work is identifying and using a coordinate system called a Common Coordinate Framework (CCF), which defines the positions, or “addresses,” in a reference body, from whole organs down to functional tissue units and individual cells. In this perspective, we examine the concept of a CCF based on the vasculature and describe why it would be an attractive choice for mapping the human body.
Highlights
When examining coordinate systems that could be used for different biological entities, specific characteristics should be considered
The vascular system has several properties that respond to the characteristics previously deemed as desirable for a CCF to enable mapping all the cells in the human body [7]. [1] It works across several scales
Because organs develop around vessels, the vasculature frames organ architecture at all scales
Summary
When examining coordinate systems that could be used for different biological entities, specific characteristics should be considered. Just as the genome map unfolds the DNA into a linear sequence, we can imagine unfolding the complex 3D twists and turns of the vasculature axis into a simpler 2D “hub-and-spoke” shape with the chambers of the heart in the center This schematic representation of the vasculature makes it easier to [1] describe location in the body; [2] align vascular pathways with varying 3D shapes but equivalent function from different people; [3] identify patterns such as changes in cell type and gene expression as one transitions from larger to smaller vessels within an organ (along a spoke); and, [4] compare tissue at the same level (e.g., capillaries) in different organs (across spokes). The exact position in 3D Cartesian space might be difficult to determine for a resected tissue specimen, the surgeon will typically be able to indicate which vascular watershed included the specimen
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