Integrated multi-omics reveals cellular and molecular interactions governing the invasive niche of basal cell carcinoma.
Laura YerlyChristine Pich-BavastroJeremy Di DomizioTania WyssStéphanie Tissot-RenaudMichael CangkramaMichel GillietSabine WernerFrançois KuonenPublished in: Nature communications (2022)
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.
Keyphrases
- single cell
- rna seq
- extracellular matrix
- high throughput
- cell therapy
- basal cell carcinoma
- poor prognosis
- mental health
- gene expression
- physical activity
- risk assessment
- oxidative stress
- climate change
- cancer therapy
- high grade
- transcription factor
- single molecule
- big data
- electronic health record
- childhood cancer
- diabetic rats
- young adults
- high glucose