Abstract
The development of functionally specialized subtypes of dendritic cells (DCs) can be modeled through the culture of bone marrow with the ligand for the cytokine receptor Flt3. Such cultures produce DCs resembling spleen plasmacytoid DCs (pDCs), CD8+ conventional DCs (cDCs) and CD8− cDCs. Here we isolated two sequential DC-committed precursor cells from such cultures: dividing 'pro-DCs', which gave rise to transitional 'pre-DCs' en route to differentiating into the three distinct DC subtypes (pDCs, CD8+ cDCs and CD8− cDCs). We also isolated an in vivo equivalent of the DC-committed pro-DC precursor cell, which also gave rise to the three DC subtypes. Clonal analysis of the progeny of individual pro-DC precursors demonstrated that some pro-DC precursors gave rise to all three DC subtypes, some produced cDCs but not pDCs, and some were fully committed to a single DC subtype. Thus, commitment to particular DC subtypes begins mainly at this pro-DC stage.
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Change history
19 October 2007
In the version of this article initially published online, the outlined boxes in the flow cytometry plots in Figure 5d are incorrect. The error has been corrected for all versions of the article.
25 October 2007
In the HTML version of this paper published online, Figure 2 was missing and a duplicate copy of Figure 4 was included in its place. This error has been corrected in the HTML version of the paper.
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Acknowledgements
We thank K. Gray and T. Berketa for animal husbandry; L. Di Rago and S. Mifsud for technical assistance with colony assays; F. Battye, F. van Diepen and the flow cytometry facilities for cell sorting and analysis; A. Keller and R. Schotte for technical assistance; and K. McIntosh for assistance with the manuscript. The Chinese hamster ovary cell line producing recombinant mouse Flt3L was provided by N. Nicola (The Walter and Eliza Hall Institute). Supported by the National Health and Medical Research Council, Australia; the Marie Curie foundation (039477 to S.H.N.); and the Korean Science and Engineering Foundation through the Medical Research Centre for Cancer Molecular Therapy, Dong-A University (J.-Y.K. and H.-Y.P.).
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S.H.N. designed and did most experiments and wrote the manuscript; K.S. designed experiments and wrote the manuscript; P.S. and H.-Y.P. isolated bone marrow precursor cells and did clonal experiments; J.-Y.K., M.O.'K. and L.W. helped to design experiments; D.M. did and analyzed colony assays; A.I.P. and A.D. assisted with precursor characterization; S.C. did the OP9 B precursor assays; M.B. and A.P. designed and did the statistical analysis; and all authors discussed the results and helped to write the manuscript.
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Naik, S., Sathe, P., Park, HY. et al. Development of plasmacytoid and conventional dendritic cell subtypes from single precursor cells derived in vitro and in vivo. Nat Immunol 8, 1217–1226 (2007). https://doi.org/10.1038/ni1522
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DOI: https://doi.org/10.1038/ni1522
