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

Miranda V. Hunter, Reuben Moncada, Joshua M. Weiss, Itai Yanai () and Richard M. White ()
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Miranda V. Hunter: Memorial Sloan Kettering Cancer Center
Reuben Moncada: NYU Langone Health
Joshua M. Weiss: Memorial Sloan Kettering Cancer Center
Itai Yanai: NYU Langone Health
Richard M. White: Memorial Sloan Kettering Cancer Center

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: 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.

Date: 2021
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DOI: 10.1038/s41467-021-26614-z

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