Single-cell RNA-seq reveals new types of human blood cells

Dendritic cells (DCs) and monocytes play a central role in pathogen sensing, phagocytosis, and antigen presentation and consist of multiple specialized subtypes. However, their identities and interrelationships are not fully understood. Using unbiased single-cell RNA sequencing (RNA-seq) of ~2400 cells, a team led by researchers at the Broad Institute of MIT and Harvard identified six human DCs and four monocyte subtypes in human blood. Their study reveals a new DC subset that shares properties with plasmacytoid DCs (pDCs) but potently activates T cells, thus redefining pDCs; a new subdivision within the CD1C+ subset of DCs; the relationship between blastic plasmacytoid DC neoplasia cells and healthy DCs; and circulating progenitor of conventional DCs (cDCs). Their revised taxonomy will enable more accurate functional and developmental analyses as well as immune monitoring in health and disease.

The research team isolated ~2400 cells enriched from the healthy human blood lineage⁻ HLA-DR⁺ compartment and subjected them to single-cell RNA sequencing. This strategy, together with follow-up profiling and functional and phenotypic characterization, led us to update the original cell classification to include six DCs, four monocyte subtypes, and one conventional DC progenitor.