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Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging
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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.
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“For example, multiplexed antibody-based imaging (mABI) technologies such as imaging mass cytometry (IMC) [31] and codetection by indexing (CODEX) [32] can detect 20–50 selected genes simultaneously in each cell at the protein level, which is a useful complement to transcript-based detection – especially given the potential for poor correlation of transcriptomic and proteomic data sets implicated”
From The heterogeneity of cellular senescence: insights at the single-cell level (2023) · cites this paper as [32]
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Metadata
- Authors
- Goltsev, Y., Samusik, N., Kennedy-Darling, J., Bhate, S., Hale, M., Vazquez, G., Black, S., & Nolan, G. P.
- Affiliations
- Stanford Medicine (US)
- Corresponding author
- Nolan, Garry P.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-08
- Volume
- 174
- Issue
- 4
- Pages
- 968-981.e15
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC6086938
- OpenAlex
- W2949238013
- Cited by
- 1,501
- References
- 20
- Citations by year
- 2026: 231 · 2025: 244 · 2024: 232 · 2023: 198 · 2022: 194 · 2021: 194 · 2020: 125 · 2019: 72 · 2018: 9
- FWCI
- 35.39
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- US NIH (U19AI057229, 1U19AI100627, R01CA184968, 1R33CA183654-01, R33CA183692, 1R01GM10983601, 1R21CA183660, 1R01NS08953301, 5UH2AR067676, 1R01CA19665701, R01HL120724, R01HL128173)
- Bill and Melinda Gates foundation (OPP1113682)
- Department of Defense (W81XWH-14-1-0180)
- Northrop-Grumman Corporation (7500108142)
- NIH (U54-CA209971)
- Rachford & Carlotta A. Harris Endowed Chair
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Keywords
- codices, splenic architecture, MRL/lpr mice, systemic lupus erythematosus, cell-cell interactions, autoimmune disease
- MeSH terms
- Animals, Antibodies, Disease Models, Animal, Female, Image Processing, Computer-Assisted, Lupus Erythematosus, Systemic, Male, Mass Spectrometry, Spleen, Oligonucleotide Probes, Mice, Inbred MRL lpr, Mice
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