Project description:Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.
Project description:Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. The human DC population comprises two main functionally-specialized lineages, whose origins and differentiation pathways remain incompletely defined. Here we combine two high-dimensional technologies — single-cell mRNA sequencing and Cytometry by Time-of-Flight (CyTOF), to identify human blood CD123+CD33+CD45RA+ DC precursors (pre-DC). Pre-DC share surface markers with plasmacytoid DC (pDC) but have distinct functional properties that were previously attributed to pDC. Tracing the differentiation of DC from the bone marrow to the peripheral blood revealed that the pre-DC compartment contains distinct lineage-committed sub-populations including one early uncommitted CD123high pre-DC subset and two CD45RA+CD123low lineage-committed subsets exhibiting functional differences. The discovery of multiple committed pre-DC populations opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.
Project description:Dendritic cells (DC) are professional antigen-presenting cells that orchestrate immune responses. Important questions on the origins and differentiation paths of human DC populations remain elusive. Here we combined two high-dimensional technologies, single-cell mRNA sequencing and mass cytometry to define and characterize CD33+CD45RA+ DC precursors (pre-DC) present in human blood. In this study, we showed that a previously understimated pre-DC population shares surface markers with plasmacytoid DC (pDC), but has distinct functional properties that were previously attributed to pDC. Finally, we trace the origin of DCs from BM to peripheral blood and reveal that pre-DC comprise three sub-populations - 1 uncommitted sub-population and 2 lineage-committed sub-populations. The discovery of committed pre-DC populations in present in human peripheral blood confirms the existence of DC as a distinct hematopoietic lineage and opens promising new avenues for the therapeutic exploitation of DC subset-specific targeting.