The Human Dendritic Cell Atlas: An integrated transcriptional tool to study human dendritic cell biology

Summary Dendritic cells (DCs) are functionally diverse and are present in most adult tissues, however progress in understanding human DC biology is hampered by a relatively small number of these in circulation and by limited access to human tissues. We built a transcriptional atlas of human DCs by combining samples from 14 expression profiling studies derived from 10 laboratories. We identified significant gene expression variation of DC subset-defining markers across tissue-type and upon viral or bacterial stimulation. We further highlight critical gaps between in vitro-derived DC subsets and their in vivo counterparts and provide evidence that monocytes or cord blood progenitor in vitro-differentiated DCs fail to capture the repertoire of primary DC subsets or behaviours. In constructing a reference DC atlas, we provide an important resource for the community wishing to identify and annotate tissue-specific DC subsets from single-cell datasets, or benchmark new in vitro models of DC biology. Key Points A reference atlas of human DC that allows benchmarking of in vitro DC models Meta-analysis of 14 integrated studies demonstrate that human conventional dendritic cells have distinct tissue-of-origin phenotypes User uploads allow tissue-relevant annotation of human DC subsets from single cell datasets Key subset markers are altered by tissue or activation status Gaps between in vitro-differentiated DC and in vivo counterparts are partially rescued by humanized mouse models, or coculture with NOTCH-ligands.