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

C Medaglia, A Giladi, L Stoler-Barak, M De Giovanni, TM Salame, A Biram, Eyal David, H Li, M Iannacone, Z Shulman, I Amit

Research output: Contribution to journalArticlepeer-review

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. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
Original languageEnglish
Pages (from-to)1622-1626
Number of pages5
JournalScience
Volume358
Issue number6370
DOIs
Publication statusPublished - 2017

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