SMART-seq2 of activated human plasmacytoid dendritic cells

Plasmacytoid and conventional dendritic cells (pDCs and cDCs, respectively) are closely related immune lineages with distinct functions. Whether pDCs can switch fate into the cDC lineage has remained controversial. Here, we sequenced purified pDCs and DCs to create a reference map of the transcriptome and chromatin landscape of all major human blood DC populations (GSE267174 and GSE267100). We compared this reference map to the transcriptomic and epigenetic profile of activated pDCs (GSE267099 and GSE266889). We show that activation of purified, bona fide human pDCs induces transcriptional and epigenetic heterogeneity at the single-cell level. A fraction of activated pDCs retains classical pDC features, while others acquire a cDC2-like identity through an intermediate state resembling transitional dendritic cells (tDCs). These datasets—generated using single-cell multiomic profiling (scRNA-seq and scATAC-seq) and SMART-seq—provide a resource to investigate the molecular basis of pDC-to-cDC2 fate transition. Human plasmacytoid dendritic cells were activated with CD40L for two days, single-cell FACS sorted and scRNA sequenced by SMARTseq2. SMARTseq2 was also performed on purified plasmacytoid and transitional dendritic cells (without activation). Sequencing was performed in two independent blood donors.