Mapping the Human DC Lineage Through the Integration of High-dimensional Techniques

Overview

Journal Science

Specialty Science

Date 2017 May 6

PMID 28473638

Citations 271

Authors

Peter See

Charles-Antoine Dutertre

Jinmiao Chen

Patrick Gunther

Naomi McGovern

Sergio Erdal Irac

Merry Gunawan

Marc Beyer

Kristian Handler

Kaibo Duan

Hermi Rizal Bin Sumatoh

Nicolas Ruffin

Mabel Jouve

Ester Gea-Mallorqui

Raoul C M Hennekam

Tony Lim

Chan Chung Yip

Ming Wen

Benoit Malleret

Ivy Low

Nurhidaya Binte Shadan

Charlene Foong Shu Fen

Alicia Tay

Josephine Lum

Francesca Zolezzi

Anis Larbi

Michael Poidinger

Jerry K Y Chan

Qingfeng Chen

Laurent Renia

Muzlifah Haniffa

Philippe Benaroch

Andreas Schlitzer

Joachim L Schultze

Evan W Newell

Florent Ginhoux

Affiliations

Soon will be listed here.

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 CD123CD33CD45RA 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 pre-DC subset and two CD45RACD123 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.

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