Comparative genomics analysis of mononuclear phagocyte subsets confirms similarity between lymphoid tissue-resident and dermal XCR1+ DCs in mouse and human and distinguishes them from Langerhans cells.
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PROVIDER: PRJNA299655 | ENA |
REPOSITORIES: ENA
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Project description:Dendritic cells (DC) are mononuclear phagocytes which exhibit a dendritic morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of specific cell surface molecules and later shown to possess distinct functions. DC subset differentiation is guided by different transcription factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations and conventional flow cytometry analysis using limited antigens is biased and potentially misleading. Moreover, the antigens currently used to define mononuclear phagocyte subsets vary depending on the tissue and animal species studied and even between laboratories. This has led to confusion in the definition of the identity of myeloid cell subsets across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC subsets and other myeloid cell types across species. We have developed a novel, simple and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. We illustrate the use of BubbleGUM by re-analyzing 3 concatenated public datasets of blood/spleen and skin/cutaneous lymph node myeloid cell subsets in humans and in mice. This analysis demonstrates the equivalence between human and mouse skin XCR1+ DCs, and between mouse and human Langerhans cells.
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Project description:Dendritic cells (DC) are mononuclear phagocytes which exhibit a branching (dendritic) morphology and excel at naïve T cell activation. DC encompass several subsets initially identified by their expression of cell surface molecules and later shown to possess distinct functions. DC subset differentiation is orchestrated by transcription factors, growth factors and cytokines. Identifying DC subsets is challenging as very few cell surface molecules are uniquely expressed on any one of these cell populations. There is no standard consensus to identify mononuclear phagocyte subsets; varying antigens are employed depending on the tissue and animal species studied and between laboratories. This has led to confusion in how to accurately define and classify DCs across tissues and between species. Here we report a comparative genomics strategy that enables universal definition of DC and other mononuclear phagocyte subsets across species. We performed a meta-analysis of several public datasets of human and mouse mononuclear phagocyte subsets isolated from blood, spleen, skin or cutaneous lymph nodes, including by using a novel and user friendly software, BubbleGUM, which generates and integrates gene signatures for high throughput gene set enrichment analysis. This analysis demonstrates the equivalence between human and mouse skin XCR1(+) DCs, and between mouse and human Langerhans cells.
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