期刊
CELL REPORTS
卷 24, 期 7, 页码 1902-+出版社
CELL PRESS
DOI: 10.1016/j.celrep.2018.07.033
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资金
- France Genomique consortium [ANR-10-INBS-0009]
- I2HD CIML-SANOFI project, INSERM, Agence Nationale de Recherches sur le SIDA et les Hepatites Virales (ANRS) [ECTZ25472]
- DCBIOL Labex - French Government's Investissements d'Avenir [ANR-11-LABEX-0043, ANR-10-IDEX-0001-02 PSL*]
- A*MIDEX project - French Government's Investissements d'Avenir [ANR-11-IDEX-0001-02]
- European Research Council under the European Community's Seventh Framework Programme (FP7/2007-2013 grant) [281225]
- NIH [AI044628, CA180913, AI081848]
- Cancer Research Institute
- Melanoma Research Alliance
- city of Marseille
- NATIONAL CANCER INSTITUTE [R01CA180913] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R37AI044628, R01AI081848, R01AI044628] Funding Source: NIH RePORTER
The ability to generate large numbers of distinct types of human dendritic cells (DCs) in vitro is critical for accelerating our understanding of DC biology and harnessing them clinically. We developed a DC differentiation method from human CD34(+) precursors leading to high yields of plasmacytoid DCs (pDCs) and both types of conventional DCs (cDC1s and cDC2s). The identity of the cells generated in vitro and their strong homology to their blood counterparts were demonstrated by phenotypic, functional, and single-cell RNA-sequencing analyses. This culture system revealed a critical role of Notch signaling and GM-CSF for promoting cDC1 generation. Moreover, we discovered a pre-terminal differentiation state for each DC type, characterized by high expression of cell-cycle genes and lack of XCR1 in the case of cDC1. Our culture system will greatly facilitate the simultaneous and comprehensive study of primary, otherwise rare human DC types, including their mutual interactions.
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