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
-
- Animals
- Disease Models, Animal
- Gene Expression Profiling
- Gene Expression Regulation, Neoplastic
- Humans
- Neoplasms/genetics*
- Neoplasms/metabolism
- RNA-Seq
- Transcriptome*
- Tumor Microenvironment*
- Zebrafish/genetics
- Zebrafish/metabolism
- PubMed
- 34725363 Full text @ Nat. Commun.
Citation
Hunter, M.V., Moncada, R., Weiss, J.M., Yanai, I., White, R.M. (2021) Spatially resolved transcriptomics reveals the architecture of the tumor-microenvironment interface. Nature communications. 12:6278.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping