Abstract

Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8α+ (CD103+) cDC1 lineage, and the CD11b+ cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the BM and seed peripheral tissues before differentiating locally into mature cDCs. Where and when commitment to the cDC1 or cDC2 lineage occurs remains poorly understood. Here we found that transcriptional signatures of the cDC1 and cDC2 lineages became evident at the single-cell level from the CDP stage. We also identified Siglec-H and Ly6C as lineage markers that distinguished pre-DC subpopulations committed to the cDC1 lineage (Siglec-HLy6C pre-DCs) or cDC2 lineage (Siglec-HLy6C+ pre-DCs). Our results indicate that commitment to the cDC1 or cDC2 lineage occurs in the BM and not in the periphery.

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Acknowledgements

We thank L. Robinson for critical review and editing of the manuscript; M.L. Ng, S.H. Tan, T.B. Lu, I. Low and N.B. Shadan for technical assistance; K. Murphy (University of Washington) for ZBTB46-GFP BM; and G. Belz (Walter & Eliza Hall Institute) for Id2-GFP BM. Supported by Singapore Immunology Network (F.G.), Agency for Science, Technology and Research (BMRC Young Investigator grant to A.S.), the Genomics Institute of Singapore (P.R.) and the Singapore Medical Research Council (NMRC/CBRG/0047/2013 to B.M.).

Author information

Author notes

    • V Sivakamasundari
    • , Jinmiao Chen
    • , Paul Robson
    •  & Florent Ginhoux

    These authors contributed equally to this work.

Affiliations

  1. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore.

    • Andreas Schlitzer
    • , Jinmiao Chen
    • , Hermi Rizal Bin Sumatoh
    • , Josephine Lum
    • , Benoit Malleret
    • , Sanqian Zhang
    • , Anis Larbi
    • , Francesca Zolezzi
    • , Laurent Renia
    • , Michael Poidinger
    • , Evan W Newell
    •  & Florent Ginhoux
  2. Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore.

    • V Sivakamasundari
    •  & Paul Robson
  3. Molecular Medicine Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.

    • Jaring Schreuder
    •  & Shalin Naik
  4. Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.

    • Benoit Malleret
  5. Department of Medical Biology, University of Melbourne, Parkville, Australia.

    • Shalin Naik

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Contributions

A.S., P.R. and F.G. conceived of the study; A.S., S.V., H.R.B.S., J.S., J.L. and B.M. performed experiments; A.S., J.C., S.Z., M.P. and F.G. analyzed data; A.L., F.Z., L.R., S.N. and E.W.N. provided reagents and intellectual guidance; and A.S., S.V., J.C. and F.G. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Florent Ginhoux.

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DOI

https://doi.org/10.1038/ni.3200

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