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Science. 2017 Dec 22;358(6370):1622-1626. doi: 10.1126/science.aao4277. Epub 2017 Dec 7.

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

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
2
Division of Immunology, Transplantation and Infectious Diseases and Experimental Imaging Center, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan 20132, Italy.
3
Flow Cytometry Unit, Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel.
4
Division of Immunology, Transplantation and Infectious Diseases and Experimental Imaging Center, IRCCS (Istituto di Ricovero e Cura a Carattere Scientifico) San Raffaele Scientific Institute and Vita-Salute San Raffaele University, Milan 20132, Italy. iannacone.matteo@hsr.it ziv.shulman@weizmann.ac.il ido.amit@weizmann.ac.il.
5
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. iannacone.matteo@hsr.it ziv.shulman@weizmann.ac.il ido.amit@weizmann.ac.il.

Abstract

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.

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PMID:
29217582
DOI:
10.1126/science.aao4277
[Indexed for MEDLINE]

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