Modular expression analysis reveals functional conservation between human Langerhans cells and mouse cross-priming dendritic cells.
Bottom Line: Transcriptional modules of coordinately expressed genes were used for defining shared functions between the species.Consistent with our analysis, LCs were highly adept at inducing primary CTL responses.Thus, our study suggests that the function of LCs may not be conserved between mouse and human and supports human LCs as an especially relevant therapeutic target.
Affiliation: Department of Pathology and Immunology and Department of Surgery/Plastic and Reconstructive Surgery Center, Washington University School of Medicine, St. Louis, MO 63110.Show MeSH
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Mentions: We took advantage of the large compendium of murine DC expression data that are available through the Immgen database. Overall, we used the WGCNA algorithm on 116 samples encompassing 36 DC subpopulations (Langfelder and Horvath, 2008) to construct and define modules. For each module, representative eigen genes could be defined that reflect the collective behavior of each module. Using this approach, we were able to define each cell type by the behavior of 16 independent modules (Fig. 2 A and Table S1). Each module represented specific components from 19 different pathways (Fig. 2 B). Modules showed a large degree of cell specificity in their expression patterns (Fig. 2 A). For example, expression of module Mm2 was enriched in the lymph node migratory populations of DCs, expression of module Mm3 was enriched in pDCs, and expression of Mm1 was specific to thymic and CD103+CD11b− small intestine subpopulations, whereas expression of Mm6 consisted of genes whose regulation was shared between the CD4+ DCs and CD103−CD11b+ skin draining lymph node. Along the same lines, module Mm16 included genes specific for CD103−CD11b+ DCs. Overall the pattern of all 16 subsets was distinct for each cell type.
Affiliation: Department of Pathology and Immunology and Department of Surgery/Plastic and Reconstructive Surgery Center, Washington University School of Medicine, St. Louis, MO 63110.