Abstract
Although much progress has been made in the understanding of the ontogeny and function of dendritic cells (DCs), the transcriptional regulation of the lineage commitment and functional specialization of DCs in vivo remains poorly understood. We made a comprehensive comparative analysis of CD8+, CD103+, CD11b+ and plasmacytoid DC subsets, as well as macrophage DC precursors and common DC precursors, across the entire immune system. Here we characterized candidate transcriptional activators involved in the commitment of myeloid progenitor cells to the DC lineage and predicted regulators of DC functional diversity in tissues. We identified a molecular signature that distinguished tissue DCs from macrophages. We also identified a transcriptional program expressed specifically during the steady-state migration of tissue DCs to the draining lymph nodes that may control tolerance to self tissue antigens.
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Acknowledgements
We thank colleagues of the ImmGen Project, especially the technical team, including M. Painter, J. Ericson and S. Davis, for contributions; C. Benoist for contributions to the design and writing of the manuscript; and eBioscience and Affymetrix for support of the ImmGen Project. Supported by the National Institute of Allergy and Infectious Diseases of the US National Institutes of Health (R24 AI072073 to the ImmGen Project (led by C. Benoist); AI080884 and HL086899 to M.M.; JDRF172010770 and DP2DK083052-01 to B.D.B.; DK074500 and AI045757 to S.J.T.; HL69438, DK056638, HL097819 and HL097700 to P.S.F.; and U54CA149145 to V.J.).
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J.C.M. did experiments and wrote the paper; M.M. designed experiments and wrote the paper; B.D.B. provided intellectual input, did computational analyses and helped write the paper; T.S. did computation analyses and identified all modules; E.L.G. purified macrophage populations and provided intellectual input; V.J. did computation analyses and, together with T.S., designed Ontogenet; A.C. and G.P. did computation analyses; M.L. did experiments; K.G.E., J.H., D.H., A.C. and J.P. purified DC populations; M.G. purified macrophage populations; M.B. and A.B.-P. purified DC and macrophage populations; P.S.F. provided intellectual input; and G.J.R. and S.J.T. provided intellectual input for experimental design.
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Supplementary Table 1
Comparison of DC subsets transcriptomes (XLSX 192 kb)
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Comparison of the transcriptome of migratory DC and tissue resident DC (XLSX 67 kb)
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Miller, J., Brown, B., Shay, T. et al. Deciphering the transcriptional network of the dendritic cell lineage. Nat Immunol 13, 888–899 (2012). https://doi.org/10.1038/ni.2370
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DOI: https://doi.org/10.1038/ni.2370
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