Format

Send to

Choose Destination
Science. 2017 Jun 9;356(6342). pii: eaag3009. doi: 10.1126/science.aag3009. Epub 2017 May 4.

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

Author information

1
Singapore Immunology Network (SIgN), A*STAR, 8A Biomedical Grove, Immunos Building, Level 4, Singapore 138648, Singapore.
2
Program in Emerging Infectious Disease, Duke-NUS Medical School, 8 College Road, 169857 Singapore.
3
Genomics and Immunoregulation, Life and Medical Sciences (LIMES) Institute, University of Bonn, 32115 Bonn, Germany.
4
Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
5
Platform for Single Cell Genomics and Epigenomics at the German Center for Neurodegenerative Diseases and the University of Bonn, 53175 Bonn, Germany.
6
Institut Curie, Paris Sciences et Lettres (PSL) Research University, INSERM U 932, F-75005, Paris, France.
7
Department of Pediatrics, Academic Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
8
Department of Anatomical Pathology, Singapore General Hospital, Singapore.
9
Department of Health Promotion Board (HPB) and Transplant Surgery, Singapore General Hospital, Singapore.
10
Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
11
Singapore Health Services Flow Cytometry Core Platform, 20 College Road, The Academia, Discovery Tower Level 10, Singapore 169856, Singapore.
12
Department of Reproductive Medicine, Division of Obstetrics and Gynaecology, KK Women's and Children's Hospital, Singapore.
13
Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore.
14
Experimental Fetal Medicine Group, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
15
Humanized Mouse Unit, Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore.
16
Myeloid Cell Biology, Life and Medical Sciences (LIMES) Institute, University of Bonn, 53115 Bonn, Germany.
17
Singapore Immunology Network (SIgN), A*STAR, 8A Biomedical Grove, Immunos Building, Level 4, Singapore 138648, Singapore. florent_ginhoux@immunol.a-star.edu.sg.

Abstract

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 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.

PMID:
28473638
DOI:
10.1126/science.aag3009
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center