Large-Scale Human Dendritic Cell Differentiation Revealing Notch-Dependent Lineage Bifurcation and Heterogeneity.
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Abstract | 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. |
Year of Publication | 2018
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Journal | Cell Rep
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Volume | 24
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Issue | 7
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Pages | 1902-1915.e6
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Date Published | 2018 08 14
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ISSN | 2211-1247
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DOI | 10.1016/j.celrep.2018.07.033
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PubMed ID | 30110645
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PubMed Central ID | PMC6113934
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Grant list | R01 AI044628 / AI / NIAID NIH HHS / United States
R01 AI081848 / AI / NIAID NIH HHS / United States
R01 CA180913 / CA / NCI NIH HHS / United States
281225 / ERC_ / European Research Council / International
R37 AI044628 / AI / NIAID NIH HHS / United States
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