PUBLICATION

Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface

Authors

Hunter, M.V., Moncada, R., Weiss, J.M., Yanai, I., White, R.M.

ID

ZDB-PUB-211103-5

Date

2021

Source

Nature communications 12: 6278 (Journal)

Registered Authors

White, Richard M.

Keywords

none

Datasets

GEO:GSE159709

MeSH Terms

RNA-Seq
Disease Models, Animal
Humans
Gene Expression Regulation, Neoplastic
Gene Expression Profiling
Zebrafish/genetics
Zebrafish/metabolism
Tumor Microenvironment*
Transcriptome*
Animals
Neoplasms/genetics*
Neoplasms/metabolism

(all 12)

PubMed

34725363 Full text @ Nat. Commun.

Abstract

During tumor progression, cancer cells come into contact with various non-tumor cell types, but it is unclear how tumors adapt to these new environments. Here, we integrate spatially resolved transcriptomics, single-cell RNA-seq, and single-nucleus RNA-seq to characterize tumor-microenvironment interactions at the tumor boundary. Using a zebrafish model of melanoma, we identify a distinct "interface" cell state where the tumor contacts neighboring tissues. This interface is composed of specialized tumor and microenvironment cells that upregulate a common set of cilia genes, and cilia proteins are enriched only where the tumor contacts the microenvironment. Cilia gene expression is regulated by ETS-family transcription factors, which normally act to suppress cilia genes outside of the interface. A cilia-enriched interface is conserved in human patient samples, suggesting it is a conserved feature of human melanoma. Our results demonstrate the power of spatially resolved transcriptomics in uncovering mechanisms that allow tumors to adapt to new environments.

Genes / Markers

Figures