Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells.
Comparative genomics analysis of mononuclear phagocyte subsets confirms homology between lymphoid tissue-resident and dermal XCR1(+) DCs in mouse and human and distinguishes them from Langerhans cells.
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DOI：
10.1016/j.jim.2016.02.023
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发表时间：
2016-05
影响因子：
2.2
通讯作者：
Dalod M
中科院分区：
文献类型：
--
作者：
Carpentier S;Vu Manh TP;Chelbi R;Henri S;Malissen B;Haniffa M;Ginhoux F;Dalod M
树突状细胞（DC）是单核吞噬细胞，其表现出分支（树突状）形态并且擅长幼稚T细胞活化。DC包括最初通过其细胞表面分子的表达鉴定的几个子集，并且后来显示具有不同的功能。DC亚群分化是由转录因子、生长因子和细胞因子协调的。识别DC亚群具有挑战性，因为很少有细胞表面分子在这些细胞群中的任何一个上独特表达。没有标准的共识来识别单核吞噬细胞亚群;根据研究的组织和动物种属以及实验室之间采用不同的抗原。这导致了如何准确地定义和分类跨组织和物种之间的DC的混乱。在这里，我们报告了一种比较基因组学策略，可以通用定义跨物种的DC和其他单核吞噬细胞亚群。我们对从血液、脾脏、皮肤或皮肤淋巴结中分离的人和小鼠单核吞噬细胞亚群的几个公共数据集进行了荟萃分析，包括使用一种新型的用户友好软件BubbleGUM，该软件生成并整合了用于高通量基因集富集分析的基因签名。该分析证明了人和小鼠皮肤XCR1 + DC之间以及小鼠和人朗格汉斯细胞之间的等效性。人CD141highXCR1+真皮DC的严格表型鉴定具有挑战性。比较基因组学使得能够严格鉴定细胞群体。人真皮CD141highXCR1 + DC与人血液和小鼠XCR1 + DC同源。人朗格汉斯细胞与小鼠朗格汉斯细胞同源。朗格汉斯细胞选择性地表达DC而不是巨噬细胞基因特征。
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. Rigorous phenotypic identification of human CD141highXCR1+ dermal DCs is challenging. Comparative genomics enables rigorous identification of cell populations. Human dermal CD141highXCR1+ DCs are homologous to human blood and mouse XCR1+ DCs. Human Langerhans cells are homologous to mouse Langerhans cells. Langerhans cells selectively express DC rather than macrophage gene signatures.