Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma

By A. Ji, Adam J. Rubin, K. Thrane, Sizun Jiang, D. Reynolds, R. Meyers, M. Guo, B. George, A. Mollbrink, J. Bergenstråhle and 11 more. Cell, 2020

999 citations recorded by the source corpus.

Summary To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.

Subfields: Immunology, Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/91c8ea00099c078d9096137f65736016f6546f21

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Huan Fu

Citations in the corpus

Benchmarking spatial and single-cell transcriptomics integration methods for transcript distribution prediction and cell type deconvolution (2022, methodology): “To evaluate the performance of the 16 integration methods, we collected 45 paired spatial transcriptomics and scRNA-seq datasets from published studies 4–7, 10, 15 , 31–”
Unsupervised spatially embedded deep representation of spatial transcriptomics (2021, background): “Such spatially resolved transcriptomes of histological tissues enable the reconstruction 49 of tissue architecture and cell-cell interactions.(1,2,3,4,5,6,7,8,9) This approach has proven 50 valuable in many applications including studies on brain disorders,(2,10) tumour 51 microenvironments,(3,11) a”