Constructing and Using Cell Type Populations of the Human Reference Atlas

The human body contains ∼27–36 trillion cells of up to 10,000 cell types (CTs) within a volume of ∼62–120 liters (males) and 52–89 liters (females). The Human Reference Atlas (HRA) v2.3 provides a quantitative 3D framework of CTs across 73 reference organs and 1,283 3D anatomical structures (ASs). The HRA Cell Type Population (HRApop) effort quantifies CTs per AS using high-quality single-cell (sc) data processed through scalable, reproducible workflows and cell type annotation (CTann) tools. HRApop v1.0 includes reference CT populations for 73 ASs (112 when sex-specific) using 662 datasets spatially registered to 230 locations across 17 organs (31 when sex-specific). For 558 sc-transcriptomics datasets (11,042,750 cells), CTs and biomarker expression were computed using Azimuth, CellTypist, and popV. To test generalizability, 104 sc-proteomics datasets (16,576,863 cells) were integrated. In total, HRApop includes 27,619,613 cells. HRApop can be used to predict (1) CT populations for 3D volumes in the human body and (2) the spatial origin of a tissue block, given a CT population. Data and code are at cns-iu.github.io/hra-cell-type-populations-supporting-information .