Large-Scale Human Dendritic Cell Differentiation Revealing Notch-Dependent Lineage Bifurcation and Heterogeneity.

Cell Rep
Authors
Keywords
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
Journal
Cell Rep
Volume
24
Issue
7
Pages
1902-1915.e6
Date Published
2018 08 14
ISSN
2211-1247
DOI
10.1016/j.celrep.2018.07.033
PubMed ID
30110645
PubMed Central ID
PMC6113934
Links
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