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Integrated multi-omics reveals the cellular and molecular interactions governing the invasive niche in skin cancer

ABSTRACT: Integrated multi-omics reveals the cellular and molecular interactions governing the invasive niche in skin cancer

PROVIDER: PRJNA753840 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15417444.fastq.gz	Fastqsanger.gz
	SRR15417445.fastq.gz	Fastqsanger.gz
	SRR15417446.fastq.gz	Fastqsanger.gz
	SRR15417447.fastq.gz	Fastqsanger.gz
	SRR17621701_1.fastq.gz	Fastqsanger.gz

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Integrated multi-omics reveals the cellular and molecular interactions governing the invasive niche in skin cancer

Project description:To progress, tumors need to invade the surrounding tissues. However, the heterogeneity of cell types at the tumor-stroma interface and the complexity of their potential interactions hampered mechanistic insights for efficient therapeutic targeting. Here, combining single-cell and spatial transcriptomics on human basal cell carcinomas (BCCs), we define the cellular contributors of the invasive front. In the invasive niche, tumor cells harbor a collective migration phenotype, supported by the expression of cell-cell junction complexes. In physical proximity, we identify cancer-associated fibroblasts (CAFs) with extracellular matrix-remodeling features, as required to support collective migration. Moreover, while tumor cells specifically express Activin A, we find Activin A-induced gene signature enrichment in adjacent CAFs subpopulations, further supporting their biological crosstalk. Altogether, our data identify the subpopulations and their transcriptional reprogramming contributing to the spatial organization of the BCC invasive niche. They also bring the proof-of-concept for integrated spatial and single-cell multi-omics to decipher cancer-specific invasive properties and develop therapeutic targeting.

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Project description:Integrated multi-omics reveals cellular and molecular interactions governing the invasive niche of basal cell carcinoma (Digital Spatial Profiling)

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Integrated multi-omics reveals cellular and molecular interactions governing the invasive niche of basal cell carcinoma.

Project description:Tumors invade the surrounding tissues to progress, but the heterogeneity of cell types at the tumor-stroma interface and the complexity of their potential interactions hampered mechanistic insight required for efficient therapeutic targeting. Here, combining single-cell and spatial transcriptomics on human basal cell carcinomas, we define the cellular contributors of tumor progression. In the invasive niche, tumor cells exhibit a collective migration phenotype, characterized by the expression of cell-cell junction complexes. In physical proximity, we identify cancer-associated fibroblasts with extracellular matrix-remodeling features. Tumor cells strongly express the cytokine Activin A, and increased Activin A-induced gene signature is found in adjacent cancer-associated fibroblast subpopulations. Altogether, our data identify the cell populations and their transcriptional reprogramming contributing to the spatial organization of the basal cell carcinoma invasive niche. They also demonstrate the power of integrated spatial and single-cell multi-omics to decipher cancer-specific invasive properties and develop targeted therapies.

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