期刊
SCIENCE
卷 358, 期 6370, 页码 1622-1626出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.aao4277
关键词
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资金
- Chan Zuckerberg Initiative
- Howard Hughes Medical Institute
- European Research Council [724471-HemTree2.0, 677713, 725038]
- Melanoma Research Alliance [509044]
- Israel Science Foundation [703/15]
- Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine
- Helen and Martin Kimmel Award for Innovative Investigation
- Minerva Stiftung
- Israeli Ministry of Science, Technology, and Space
- David and Fela Shapell Family Foundation
- NeuroMac DFG (German Research Foundation)/Transregional Collaborative Research Center
- Abramson Family Center for Young Scientists
- Morris Kahn Institute for Human Immunology and Human Frontiers of Science Program [CDA-00023/2016]
- Azrieli Foundation
- Rising Tide Foundation
- Benoziyo Endowment Fund for the Advancement of Science
- Comisaroff Family Trust
- Irma and Jacques Ber-Lehmsdorf Foundation
- Gerald O. Mann Charitable Foundation
- David M. Polen Charitable Trust
- Italian Association for Cancer Research [15350]
- Italian Ministry of Health [GR-2011-02347925]
- Fondazione Regionale per la Ricerca Biomedica [2015-0010]
- European Molecular Biology Organization
- Giovanni Armenise-Harvard Foundation
- Clore Fellowship
- Marie Curie Individual Fellowship (European Union) (SCALTIE) [746382]
- Marie Curie Actions (MSCA) [746382] Funding Source: Marie Curie Actions (MSCA)
- European Research Council (ERC) [677713, 725038] Funding Source: European Research Council (ERC)
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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