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

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.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Moncada R,Barkley D,Wagner F,Chiodin M,Devlin JC,Baron M,Hajdu CH,Simeone DM,Yanai I

doi

10.1038/s41587-019-0392-8

subject

Has Abstract

pub_date

2020-03-01 00:00:00

pages

333-342

issue

3

eissn

1087-0156

issn

1546-1696

pii

10.1038/s41587-019-0392-8

journal_volume

38

pub_type

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