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

Authors
  • Medaglia, Chiara1
  • Giladi, Amir1
  • Stoler-Barak, Liat1
  • De Giovanni, Marco2
  • Salame, Tomer Meir3
  • Biram, Adi1
  • David, Eyal1
  • Li, Hanjie1
  • Iannacone, Matteo4
  • Shulman, Ziv5
  • Amit, Ido5
  • 1 Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. , (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. , (Italy)
  • 3 Flow Cytometry Unit, Department of Biological Services, Weizmann Institute of Science, Rehovot, Israel. , (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. [email protected] [email protected] [email protected] , (Italy)
  • 5 Department of Immunology, Weizmann Institute of Science, Rehovot, Israel. [email protected] [email protected] [email protected] , (Israel)
Type
Published Article
Journal
Science
Publisher
American Association for the Advancement of Science (AAAS)
Publication Date
Dec 22, 2017
Volume
358
Issue
6370
Pages
1622–1626
Identifiers
DOI: 10.1126/science.aao4277
PMID: 29217582
Source
Medline
License
Unknown

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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