Cited by 1,045Single-cell and spatial transcriptomicsPancreatic and Hepatic Oncology ResearchGene expression and cancer classification

Integrating microarray-based spatial transcriptomics and single-cell RNA-seq reveals tissue architecture in pancreatic ductal adenocarcinomas

Moncada, Reuben, Barkley, Dalia, Wagner, Florian, Chiodin, Marta, Devlin, Joseph C., Baron, Maayan, Hajdu, Cristina H., Simeone, Diane M. +1 more·2020·Nature Biotechnology

Abstract

Single-cell RNA sequencing (scRNA-seq) enables the systematic identification of cell populations in a tissue, but characterizing their spatial organization remains challenging. We combine a microarray-based spatial transcriptomics method that reveals spatial patterns of gene expression using an array of spots, each capturing the transcriptomes of multiple adjacent cells, with scRNA-Seq generated from the same sample. To annotate the precise cellular composition of distinct tissue regions, we introduce a method for multimodal intersection analysis. Applying multimodal intersection analysis to primary pancreatic tumors, we find that subpopulations of ductal cells, macrophages, dendritic cells and cancer cells have spatially restricted enrichments, as well as distinct coenrichments with other cell types. Furthermore, we identify colocalization of inflammatory fibroblasts and cancer cells expressing a stress-response gene module. Our approach for mapping the architecture of scRNA-seq-defined subpopulations can be applied to reveal the interactions inherent to complex tissues.

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Crossref · 10.1038/s41587-019-0392-8

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Authors
Moncada, R., Barkley, D., Wagner, F., Chiodin, M., Devlin, J. C., Baron, M., Hajdu, C. H., Simeone, D. M., & Yanai, I.
Affiliations
NYU Langone Health (US)
Corresponding author
Yanai, Itai
Venue
Nature Biotechnology
Published
2020-01-13
Volume
38
Issue
3
Pages
333-342
ISSN
  • 0733-222X (ISSN-L)
  • 1087-0156
  • 1546-1696
OpenAlex
W2999977864
Cited by
1,045
References
10
Citations by year
2026: 163 · 2025: 197 · 2024: 211 · 2023: 147 · 2022: 173 · 2021: 105 · 2020: 49
FWCI
39.42
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Biotechnology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
  • Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene expression and cancer classification
Keywords
pancreatic ductal adenocarcinoma, spatial transcriptomics, single-cell RNA sequencing, tissue structure, tumor microenvironment, macrophages, dendritic cells, inflammatory fibroblasts, tumor cell subpopulations, cell-cell interactions
MeSH terms
Dendritic Cells, Humans, Macrophages, Pancreatectomy, Pancreatic Neoplasms, Gene Expression Regulation, Neoplastic, Sequence Analysis, RNA, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Carcinoma, Pancreatic Ductal, Gene Regulatory Networks, Single-Cell Analysis, Spatio-Temporal Analysis

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