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

被引：112

作者：

Balan, Sreekumar ^{[1
,2
,3
]}

Arnold-Schrauf, Catharina ^{[1
]}

Abbas, Abdenour ^{[1
]}

Couespel, Norbert ^{[1
]}

Savoret, Juliette ^{[1
]}

Imperatore, Francesco ^{[1
]}

Villani, Alexandra-Chloe ^{[4
,5
]}

Thien-Phong Vu Manh ^{[1
]}

Bhardwaj, Nina ^{[2
,3
]}

Dalod, Marc ^{[1
]}

机构：

[1] Aix Marseille Univ, CIML, INSERM, CNRS, F-13288 Marseille, France

[2] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA

[3] Parker Inst Canc Immunotherapy, San Francisco, CA 94129 USA

[4] Brd Inst Harvard Univ & MIT, Cambridge, MA 02142 USA

[5] Massachusetts Gen Hosp, Ctr Immunol & Inflammatory Dis, Boston, MA 02129 USA

来源：

CELL REPORTS | 2018年 / 24卷 / 07期

基金：

欧洲研究理事会;

关键词：

MELANOMA PATIENTS; BONE-MARROW; STEM-CELLS; IN-VITRO; BLOOD; PROGENITORS; EXPRESSION; RECEPTOR; VACCINES; MOUSE;

D O I：

10.1016/j.celrep.2018.07.033

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1902 / +

页数：20

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