Journal Article

Mapping the human DC lineage through the integration of high-dimensional techniques

Chen, Qingfeng, Benaroch, Philippe, Schlitzer, Andreas, Newell, Evan W., See, Peter, Schultze, Joachim L., Shadan, Nurhidaya Binte, Hennekam, Raoul C. M., Duan, Kaibo, Ginhoux, Florent, Irac, Sergio Erdal, Ruffin, Nicolas, Lum, Josephine, Beyer, Marc, Low, Ivy, Haniffa, Muzlifah, Zolezzi, Francesca, Dutertre, Charles-Antoine, Günther, Patrick, Gunawan, Merry, Larbi, Anis, Rénia, Laurent, Wen, Ming, Jouve, Mabel, Malleret, Benoit, Poidinger, Michael, Chan, Jerry K. Y., Chen, Jinmiao, Sumatoh, Hermi Rizal Bin, Gea-Mallorquí, Ester, Lim, Tony, Fen, Charlene Foong Shu, Händler, Kristian, McGovern, Naomi, Yip, Chan Chung, Tay, Alicia

2017

Overview

Dendritic cells (DCs) are important components of the immune system that form from the bone marrow into two major cell lineages: plasmacytoid DCs and conventional DCs. See et al. applied single-cell RNA sequencing and cytometry by time-of-flight to characterize the developmental pathways of these cells. They identified blood DC precursors that shared surface markers with plasmacytoid DCs but that were functionally distinct. This unsuspected level of complexity in pre-DC populations reveals additional cell types and refines understanding of known cell types. Science , this issue p. eaag3009 In human blood, the immunological dendritic cell lineage contains many predendritic cell populations. 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 messenger RNA sequencing (scmRNAseq) 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 subpopulations, including one early uncommitted CD123 high pre-DC subset and two CD45RA + CD123 low 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.

• Publisher: American Association for the Advancement of Science,The American Association for the Advancement of Science
• Subject: Antigen-presenting cells / Antigens / Biomarkers / Blood / Blood Cells - cytology / Bone marrow / CD123 antigen / CD1c antigen / CD4 antigen / CD45RA antigen / CD5 antigen / Cdc2 protein / Cell Differentiation / Cell Lineage / Cell proliferation / Cell Separation - methods / Complexity / Costimulator / CpG islands / CX3CR1 protein / Dendritic cells / Dendritic Cells - cytology / Dendritic structure / Differentiation / Exploitation / Flow cytometry / Gene sequencing / Hemopoiesis / Homeostasis / Humans / Immune response / Immune system / Individualized Instruction / Interferon / Interleukin 12 / Lymphocytes / Lymphocytes T / Mapping / Markers / Microfluidics / Origins / Pathways / Population / Populations / Precursors / RESEARCH ARTICLE SUMMARY / Sequence Analysis, RNA / Single-Cell Analysis / Spleen / Stem cells / Subpopulations / Surface markers / T cell receptors / Toll-like receptors / Unsupervised Machine Learning