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Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging

Goltsev, Yury ; Samusik, Nikolay ; Kennedy-Darling, Julia ; Bhate, Salil ; Hale, Matthew ; Vazquez, Gustavo ; Black, Sarah ; Nolan, Garry P.

Cell, 2018-08, Vol.174 (4), p.968-981.e15 [Periódico revisado por pares]

United States: Elsevier Inc

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  • Título:
    Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging
  • Autor: Goltsev, Yury ; Samusik, Nikolay ; Kennedy-Darling, Julia ; Bhate, Salil ; Hale, Matthew ; Vazquez, Gustavo ; Black, Sarah ; Nolan, Garry P.
  • Assuntos: Animals ; Antibodies - chemistry ; autoimmunity ; CODEX ; Disease Models, Animal ; Female ; Image Processing, Computer-Assisted - methods ; immune tissue ; Lupus Erythematosus, Systemic - pathology ; Male ; Mass Spectrometry ; Mice ; Mice, Inbred MRL lpr ; microenvironment ; multidimensional imaging ; multiplexed imaging ; niche ; Oligonucleotide Probes - chemistry ; Spleen - pathology ; tissue architecture
  • É parte de: Cell, 2018-08, Vol.174 (4), p.968-981.e15
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
    content type line 23
    Present address: Smart Tube, Inc., 922 Industrial Avenue, Palo Alto, CA 94303, USA
    Lead Contact
    These authors contributed equally
  • Descrição: A highly multiplexed cytometric imaging approach, termed co-detection by indexing (CODEX), is used here to create multiplexed datasets of normal and lupus (MRL/lpr) murine spleens. CODEX iteratively visualizes antibody binding events using DNA barcodes, fluorescent dNTP analogs, and an in situ polymerization-based indexing procedure. An algorithmic pipeline for single-cell antigen quantification in tightly packed tissues was developed and used to overlay well-known morphological features with de novo characterization of lymphoid tissue architecture at a single-cell and cellular neighborhood levels. We observed an unexpected, profound impact of the cellular neighborhood on the expression of protein receptors on immune cells. By comparing normal murine spleen to spleens from animals with systemic autoimmune disease (MRL/lpr), extensive and previously uncharacterized splenic cell-interaction dynamics in the healthy versus diseased state was observed. The fidelity of multiplexed spatial cytometry demonstrated here allows for quantitative systemic characterization of tissue architecture in normal and clinically aberrant samples. [Display omitted] •Autoimmunity analyzed by multiplexed DNA-tagged antibody staining (CODEX)•CODEX data reveal pairwise interactions and niches changing with disease•First tier of neighbors significantly impacts marker expression in the index cells•Changes in splenic morphology correlate with shifts in cell frequencies A DNA barcoding-based imaging technique uses multiplexed tissue antigen staining to enable the characterization of cell types and dynamics in a model of autoimmune disease.
  • Editor: United States: Elsevier Inc
  • Idioma: Inglês
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