The Human Dendritic Cell Atlas: An Integrated Transcriptional Tool to Study Human Dendritic Cell Biology

Abstract

Dendritic cells (DCs) are functionally diverse and are present in most adult tissues, but deep understanding of human DC biology is hampered by relatively small numbers of these in circulation and their short lifespan in 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 behaviors. 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.

FcRn regulates antigen presentation in dendritic cells downstream of DEC205-targeted vaccines

“…1B ). To evaluate FcRn in human DCs, we used the Human DC Atlas 37 , 38 . FCGRT expression was expressed by both human blood-derived cDC1 and cDC2 without stimulation and ex vivo incubation of DCs with bacterial or viral stimuli did not alter FCGRT expression for either subset (Supplementary Fig.…”

Efficient generation of human dendritic cells from iPSC by introducing a feeder-free expansion step for hematopoietic progenitors

“…We asked whether genes that exhibit distinct expression patterns in iPSC-DC subsets also demonstrate subset-specificity across DC subsets derived in vivo . Our analysis, leveraging the Human DC Atlas database (40), revealed that most of these genes do not display subset-discriminating patterns among in vivo DCs (Supp. Figure 2A).…”

“… A) Heatmap of the top 10 DE genes expressed by iPSC-DC subsets compared between the reference Human DC Atlas (40) cell types. The genes identified with p_adjust (BH)<0.01 and ranked with logFC among iPSC-DC subsets.…”