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Figure S1. Summary of origins and context-dependent fate of murine monocytes. In this study, we establish MDPs as in vivo precursors of Gr1^low and Gr1^high BM and blood monocytes. Gr1^high monocytes can differentiate in the BM into Gr1^low monocytes. However, it remains to be determined whether they are an obligatory intermediate for Gr1^- monocyte generation and whether the conversion to Gr1^low monocytes is restricted to the bone marrow. Once released into the blood, Gr1^high monocytes have three potential fates: (a) to return to the BM and contribute to the generation of Gr1^- monocytes and potentially BM-resident and peripheral MPs; (b) to be recruited by chemokines, such as MCP-1, and to sites of inflammation, including the skin (Palframan, R.T., S. Jung, G. Cheng, W. Weninger, Y. Luo, M. Dorf, D.R. Littman, B.J. Rollins, H. Zweerink, A. Rot, and U.H. von Andrian. 2001. J. Exp. Med. 194:1361–1373; and Geissmann, F., S. Jung, and D.R. Littman. 2003. Immunity. 19:71–82); and (c) to contribute to the replenishment of intestinal and lung lamina propria MPs, including MΦs and DCs. Importantly, the conversion of Gr1^high monocytes into Gr1^low cells precludes drawing the conclusion that Gr1^high monocyte subsets are direct precursors of the intestinal and lung DCs. Notably, the CCR2^- rat monocyte subset (Yrlid, U., C.D. Jenkins, and G.G. MacPherson. 2006. J. Immunol. 176:4155–4162) and the murine Gr1^low blood monocytes have the potential to give rise to DCs (unpublished data). We show that monocytes that home to the spleen give rise to CD11c^int cells but fail to differentiate in the absence of inflammation into CD11c^high DCs. Instead, DC maintenance in this organ seems in resting state to rely on local precursors, such as MDPs or the recently identified pre-cDCs (Naik, S.H., D. Metcalf, A. van Nieuwenhuijze, I. Wicks, L. Wu, M. O’Keeffe, and K. Shortman. 2006. Nat. Immunol. 7:663–671), which differentiate without a monocytic intermediate into CD8α⁺ and CD11b⁺ DCs.