Authors: Goltsev Y, Samusik N,
Kennedy-Darling J, Bhate S, Hale M, Vazquez G, Black S, Nolan GP
Issue: Cell 2018 Aug; 174(4):968-981.e15
PMID: 30078711
Abstract:
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.