Spatial reconstruction of immune niches by combining photoactivatable reporters and scRNA-seq

被引：205

作者：

Medaglia, Chiara ^{[1
]}

Giladi, Amir ^{[1
]}

Stoler-Barak, Liat ^{[1
]}

De Giovanni, Marco ^{[2
,3
,4
]}

Salame, Tomer Meir ^{[5
]}

Biram, Adi ^{[1
]}

David, Eyal ^{[1
]}

Li, Hanjie ^{[1
]}

Iannacone, Matteo ^{[2
,3
,4
]}

Shulman, Ziv ^{[1
]}

Amit, Ido ^{[1
]}

机构：

[1] Weizmann Inst Sci, Dept Immunol, Rehovot, Israel

[2] Ist Sci San Raffaele, IRCCS, Div Immunol Transplantat & Infect Dis, I-20132 Milan, Italy

[3] Ist Sci San Raffaele, IRCCS, Expt Imaging Ctr, I-20132 Milan, Italy

[4] Univ Vita Salute San Raffaele, I-20132 Milan, Italy

[5] Weizmann Inst Sci, Dept Biol Serv, Flow Cytometry Unit, Rehovot, Israel

来源：

SCIENCE | 2017年 / 358卷 / 6370期

基金：

以色列科学基金会; 欧洲研究理事会;

关键词：

GENE-EXPRESSION; SINGLE CELLS; HETEROGENEITY;

D O I：

10.1126/science.aao4277

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Cellular functions are strongly dependent on surrounding cells and environmental factors. Current technologies are limited in their ability to characterize the spatial location and gene programs of cells in poorly structured and dynamic niches. We developed a method, NICHE-seq, that combines photoactivatable fluorescent reporters, two-photon microscopy, and single-cell RNA sequencing (scRNA-seq) to infer the cellular and molecular composition of niches. We applied NICHE-seq to examine the high-order assembly of immune cell networks. NICHE-seq is highly reproducible in spatial tissue reconstruction, enabling identification of rare niche-specific immune subpopulations and gene programs, including natural killer cells within infected B cell follicles and distinct myeloid states in the spleen and tumor. This study establishes NICHE-seq as a broadly applicable method for elucidating high-order spatial organization of cell types and their molecular pathways.

引用

页码：1622 / 1626

页数：5

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