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.
Competing Interest Statement
The authors have declared no competing interest.