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

Lookup NU author(s): Dr Merry Gunawan, Professor Muzlifah Haniffa

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This is the authors' accepted manuscript of an article that has been published in its final definitive form by American Association for the Advancement of Science, 2017.

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Abstract

© 2017 American Association for the Advancement of Science. 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 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.

Publication metadata

Author(s): See P, Dutertre C-A, Chen J, Gunther P, McGovern N, Irac SE, Gunawan M, Beyer M, Handler K, Duan K, Sumatoh HRB, Ruffin N, Jouve M, Gea-Mallorqui E, Hennekam RCM, Lim T, Yip CC, Wen M, Malleret B, Low I, Shadan NB, Fen CFS, Tay A, Lum J, Zolezzi F, Larbi A, Poidinger M, Chan JKY, Chen Q, Renia L, Haniffa M, Benaroch P, Schlitzer A, Schultze JL, Newell EW, Ginhoux F

Publication type: Article

Publication status: Published

Journal: Science

Year: 2017

Volume: 356

Issue: 6339

Pages: 1-23

Print publication date: 19/05/2017

Online publication date: 04/05/2017

Acceptance date: 25/04/2017

Date deposited: 07/07/2017

ISSN (print): 0036-8075

ISSN (electronic): 1095-9203

Publisher: American Association for the Advancement of Science

URL: https://doi.org/10.1126/science.aag3009

DOI: 10.1126/science.eaag3009

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