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

  • Peter See
  • , Charles-Antoine Dutertre
  • , Jinmiao Chen
  • , Patrick Günther
  • , Naomi McGovern
  • , Sergio Erdal Irac
  • , Merry Gunawan
  • , Marc Beyer
  • , Kristian Händler
  • , Kaibo Duan
  • , Hermi Rizal Bin Sumatoh
  • , Nicolas Ruffin
  • , Mabel Jouve
  • , Ester Gea-Mallorquí
  • , 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 Rénia, Muzlifah Haniffa, Philippe Benaroch, Andreas Schlitzer, Joachim L. Schultze, Evan W. Newell, Florent Ginhoux

Research output: Contribution to journalArticleAcademicpeer-review

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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
Original languageEnglish
Pages (from-to)1044-+
JournalScience
Volume356
Issue number6342
DOIs
Publication statusPublished - 2017

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