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Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow

Nature Immunology volume 8, pages 1207–1216 (2007)Cite this article

Abstract

Lymphoid tissue plasmacytoid and conventional dendritic cells (DCs) are continuously regenerated from hematopoietic stem cells. The cytokine dependence and biology of plasmacytoid and conventional DCs suggest that regeneration might proceed through common DC-restricted developmental intermediates. By selecting for cytokine receptor expression relevant to DC development, we identify here highly cycling Lin−c-KitintFlt3+M-CSFR+ cells with a distinct gene-expression profile in mouse bone marrow that, on a clonal level in vitro and as a population both in vitro and in vivo, efficiently generated plasmacytoid and conventional DCs but no other lineages, which increased in number after in vivo injection of the cytokine Flt3 ligand. These clonogenic common DC progenitors thus define a cytokine-regulated DC developmental pathway that ensures the supply of various DC populations.

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Figure 1: Identification of Lin−c-KitintFlt3+M-CSFR+ progenitor cells in mouse bone marrow.
Figure 2: Lin−c-KitintFlt3+M-CSFR+ progenitors generate pDCs and cDCs in vitro.
Figure 3: Single Lin−c-KitintFlt3+M-CSFR+ cells generate both pDCs and cDCs.
Figure 4: M-CSF acts together with Flt3L in the expansion of pDC populations from Lin−c-KitintFlt3+M-CSFR+ cells.
Figure 5: Lin−c-KitintFlt3+M-CSFR+ cells differentiate into pDCs and cDCs in lethally irradiated mice in vivo.
Figure 6: Lin−c-KitintFlt3+M-CSFR+ cells develop into functional pDCs and cDCs in vivo.
Figure 7: Expression profiles of lineage- and differentiation-affiliated genes.

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Acknowledgements

Supported by the Swiss National Science Foundation (310000-116637), the Deutsche Forschungsgemeinschaft (MA 2159/2-1) and the European Commission FP6 Network of Excellence initiative (LSHB-CT-2004-512074 DC-THERA).

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Author notes

  1. Nobuyuki Onai and Aya Obata-Onai: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute for Research in Biomedicine, Bellinzona, CH-6500, Switzerland

    Nobuyuki Onai, Aya Obata-Onai, Michael A Schmid, David Jarrossay & Markus G Manz

  2. Department of Immunology, Akita University Graduate School of Medicine, Akita, 010-8543, Japan

    Nobuyuki Onai, Aya Obata-Onai & Toshiaki Ohteki

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  1. Nobuyuki Onai
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Contributions

N.O., A.O.-O. and M.A.S. designed experiments, did experiments, collected data and contributed to the writing of the manuscript; T.O. provided advice; D.J. did cell sorting; and M.G.M. directed the study and wrote the manuscript.

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Correspondence to Markus G Manz.

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Onai, N., Obata-Onai, A., Schmid, M. et al. Identification of clonogenic common Flt3+M-CSFR+ plasmacytoid and conventional dendritic cell progenitors in mouse bone marrow. Nat Immunol 8, 1207–1216 (2007). https://doi.org/10.1038/ni1518

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