Blood is the predominant source for molecular analyses in humans, both in clinical and research settings, and is the target for many therapeutic strategies, emphasizing the need for comprehensive molecular maps of the cells constituting human blood. The Human Protein Atlas program (www.proteinatlas.org) is an open-access database that aims to map all human proteins by integrating various omics technologies, including antibody-based imaging. Previously, the Human Protein Atlas included gene expression information from peripheral blood mononuclear cells but not the many subpopulations of blood cells within this cell type. To increase the resolution, we performed an in-depth characterization of the constituent cells in blood to provide a detailed view of the gene expression in individual human blood cells and relate these to the other tissues in the body.

A quantitative transcriptomics-based expression analysis was performed in 18 canonical immune cell populations (Fig. 1) isolated by flow cytometric sorting. The blood cell expression profiles are presented in combination with expression profiles of tissues, including transcriptomics data from external sources to expand the number of tissue types as well as brain regions included in the database. A genome-wide classification of the protein-coding genes has been performed in terms of expression specificity and distribution, both in blood cells and tissues.

We present an atlas of the expression of all protein-coding genes in human blood cells, integrated with a classification of the specificity and distribution of all protein-coding genes in all major tissues and organs in the human body. A genome-wide analysis of blood cell RNA expression profiles allowed the identification of genes with elevated expression in various immune cells, confirming well-known protein markers, but also identified novel targets for in-depth analysis. There are 1448 protein-coding genes that have enriched expression in a single immune cell type. It will be interesting to study the corresponding proteins further to explore the biological functions linked to the respective cell phenotypes. A network plot of all cell type–enriched and group-enriched genes (Fig. 1B) reveals that many of the cell type–enriched genes are in neutrophils, eosinophils, and plasmacytoid dendritic cells, while many of the elevated genes in T and B cells are group-enriched across subpopulations of these lymphocytes. To illustrate the usefulness of this resource, we show the cellular distribution of genes known to cause primary immunodeficiencies in humans and find that many of these genes are expressed in cells not currently implicated in these diseases, illustrating how this global atlas can help us better understand the function of specific genes across cells and tissues in humans.

In this study, we have performed a genome-wide transcriptomic analysis of protein-coding genes in sorted blood immune cell populations to characterize the expression levels of each individual gene across all cell types. All data are presented in an interactive, open-access Blood Atlas as part of the Human Protein Atlas and are integrated with expression profiles across all major tissues to provide spatial classification of all protein-coding genes. This allows for a genome-wide exploration of the expression profiles across human immune cell populations and all major human tissues and organs.

(A) A schematic view of the hematopoietic differentiation. This study analyzes the cell types shown in the bottom row. NK, natural killer. (B) Network plot showing the …