Novel insights into the relationships between dendritic cell subsets in human and mouse revealed by genome-wide expression profiling

被引:398
作者
Robbins, Scott H. [1 ,2 ,3 ]
Walzer, Thierry [1 ,2 ,3 ]
Dembele, Doulaye [4 ,5 ]
Thibault, Christelle [4 ,5 ]
Defays, Axel [1 ,2 ,3 ]
Bessou, Gilles [1 ,2 ,3 ]
Xu, Huichun [6 ]
Vivier, Eric [1 ,2 ,3 ,7 ]
Sellars, MacLean [4 ,5 ]
Pierre, Philippe [1 ,2 ,3 ]
Sharp, Franck R. [6 ]
Chan, Susan [4 ,5 ]
Kastner, Philippe [4 ,5 ]
Dalod, Marc [1 ,2 ,3 ]
机构
[1] Univ Mediterranee, CIML, F-13288 Marseille, France
[2] INSERM, U631, F-13288 Marseille, France
[3] CNRS, UMR 6102, F-13288 Marseille, France
[4] IGBMC, F-67400 Illkirch Graffenstaden, France
[5] Univ Strasbourg, UM41, F-67400 Strasbourg, France
[6] Univ Calif Davis, Med Ctr, Med Invest Neurodev Disorder Inst, Sacramento, CA 95817 USA
[7] Hop Conception, Assistance Publ Hop Marshille, F-13385 Marseille, France
基金
澳大利亚研究理事会;
关键词
D O I
10.1186/gb-2008-9-1-r17
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Background: Dendritic cells (DCs) are a complex group of cells that play a critical role in vertebrate immunity. Lymph-node resident DCs (LN-DCs) are subdivided into conventional DC (cDC) subsets (CD11b and CD8a in mouse; BDCA1 and BDCA3 in human) and plasmacytoid DCs (pDCs). It is currently unclear if these various DC populations belong to a unique hematopoietic lineage and if the subsets identified in the mouse and human systems are evolutionary homologs. To gain novel insights into these questions, we sought conserved genetic signatures for LN-DCs and in vitro derived granulocyte-macrophage colony stimulating factor (GM-CSF) DCs through the analysis of a compendium of genome-wide expression profiles of mouse or human leukocytes. Results: We show through clustering analysis that all LN-DC subsets form a distinct branch within the leukocyte family tree, and reveal a transcriptomal signature evolutionarily conserved in all LN-DC subsets. Moreover, we identify a large gene expression program shared between mouse and human pDCs, and smaller conserved profiles shared between mouse and human LN-cDC subsets. Importantly, most of these genes have not been previously associated with DC function and many have unknown functions. Finally, we use compendium analysis to re-evaluate the classification of interferon-producing killer DCs, lin-CD16(+)HLA-DR+ cells and in vitro derived GM-CSF DCs, and show that these cells are more closely linked to natural killer and myeloid cells, respectively. Conclusion: Our study provides a unique database resource for future investigation of the evolutionarily conserved molecular pathways governing the ontogeny and functions of leukocyte subsets, especially DCs.
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页数:27
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