Identification of cDC1-and cDC2-committed DC progenitors reveals early lineage priming at the common DC progenitor stage in the bone marrow

被引:409
作者
Schlitzer, Andreas [1 ]
Sivakamasundari, V. [2 ]
Chen, Jinmiao [1 ]
Bin Sumatoh, Hermi Rizal [1 ]
Schreuder, Jaring [3 ]
Lum, Josephine [1 ]
Malleret, Benoit [1 ,4 ]
Zhang, Sanqian [1 ]
Larbi, Anis [1 ]
Zolezzi, Francesca [1 ]
Renia, Laurent [1 ]
Poidinger, Michael [1 ]
Naik, Shalin [3 ,5 ]
Newell, Evan W. [1 ]
Robson, Paul [2 ]
Ginhoux, Florent [1 ]
机构
[1] Agcy Sci Technol & Res, Si3gapore Immunol Network, Singapore, Singapore
[2] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore
[3] Royal Melbourne Hosp, Walter & Eliza Hall Inst Med Res, Div Mol Med, Parkville, Vic 3050, Australia
[4] Natl Univ Singapore, Yong Loo Lin Sch Med, Natl Univ Hlth Syst, Dept Microbiol, Singapore 117595, Singapore
[5] Univ Melbourne, Dept Med Biol, Parkville, Vic 3052, Australia
基金
英国医学研究理事会;
关键词
HEMATOPOIETIC STEM-CELLS; CLASSICAL DENDRITIC CELLS; TRANSCRIPTION-FACTOR; COMMITTED PROGENITORS; LYMPHOID-TISSUE; HOMEOSTASIS; EXPRESSION; RECEPTOR; MOUSE; DYNAMICS;
D O I
10.1038/ni.3200
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Mouse conventional dendritic cells (cDCs) can be classified into two functionally distinct lineages: the CD8 alpha(+) (CD103(+)) cDC1 lineage, and the CD11b(+) cDC2 lineage. cDCs arise from a cascade of bone marrow (BM) DC-committed progenitor cells that include the common DC progenitors (CDPs) and pre-DCs, which exit the BM and seed peripheral tissues before differentiating locally into mature cDCs. Where and when commitment to the cDC1 or cDC2 lineage occurs remains poorly understood. Here we found that transcriptional signatures of the cDC1 and cDC2 lineages became evident at the single-cell level from the CDP stage. We also identified Siglec-H and Ly6C as lineage markers that distinguished pre-DC subpopulations committed to the cDC1 lineage (Siglec-H(-)Ly6C(-)pre-DCs) or cDC2 lineage (Siglec-H(-)Ly6C(+) pre-DCs). Our results indicate that commitment to the cDC1 or cDC2 lineage occurs in the BM and not in the periphery.
引用
收藏
页码:718 / +
页数:13
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