» Articles » PMID: 39529126

SpottedPy Quantifies Relationships Between Spatial Transcriptomic Hotspots and Uncovers Environmental Cues of Epithelial-mesenchymal Plasticity in Breast Cancer

Overview
Journal Genome Biol
Specialties Biology
Genetics
Date 2024 Nov 11
PMID 39529126
Authors
Affiliations
Soon will be listed here.
Abstract

Spatial transcriptomics is revolutionizing the exploration of intratissue heterogeneity in cancer, yet capturing cellular niches and their spatial relationships remains challenging. We introduce SpottedPy, a Python package designed to identify tumor hotspots and map spatial interactions within the cancer ecosystem. Using SpottedPy, we examine epithelial-mesenchymal plasticity in breast cancer and highlight stable niches associated with angiogenic and hypoxic regions, shielded by CAFs and macrophages. Hybrid and mesenchymal hotspot distribution follows transformation gradients reflecting progressive immunosuppression. Our method offers flexibility to explore spatial relationships at different scales, from immediate neighbors to broader tissue modules, providing new insights into tumor microenvironment dynamics.

References
1.
Lengrand J, Pastushenko I, Vanuytven S, Song Y, Venet D, Sarate R . Pharmacological targeting of netrin-1 inhibits EMT in cancer. Nature. 2023; 620(7973):402-408. PMC: 7615210. DOI: 10.1038/s41586-023-06372-2. View

2.
Datar I, Schalper K . Epithelial-Mesenchymal Transition and Immune Evasion during Lung Cancer Progression: The Chicken or the Egg?. Clin Cancer Res. 2016; 22(14):3422-4. PMC: 4947415. DOI: 10.1158/1078-0432.CCR-16-0336. View

3.
Kumar T, Nee K, Wei R, He S, Nguyen Q, Bai S . A spatially resolved single-cell genomic atlas of the adult human breast. Nature. 2023; 620(7972):181-191. PMC: 11443819. DOI: 10.1038/s41586-023-06252-9. View

4.
Palla G, Spitzer H, Klein M, Fischer D, Schaar A, Kuemmerle L . Squidpy: a scalable framework for spatial omics analysis. Nat Methods. 2022; 19(2):171-178. PMC: 8828470. DOI: 10.1038/s41592-021-01358-2. View

5.
Turley S, Cremasco V, Astarita J . Immunological hallmarks of stromal cells in the tumour microenvironment. Nat Rev Immunol. 2015; 15(11):669-82. DOI: 10.1038/nri3902. View