Department of Dermatology and Venereology, Hôpital de Beaumont, Lausanne University Hospital Center, 1011, Lausanne, Switzerland.
Bioinformatics Core Facility (BCF), Swiss Institute of Bioinformatics, Quartier UniL-Sorge, Bâtiment Amphipole, 1015, Lausanne, Switzerland.
Nat Commun. 2022 Aug 20;13(1):4897. doi: 10.1038/s41467-022-32670-w.
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.
肿瘤通过浸润周围组织来进展，但肿瘤-基质界面处细胞类型的异质性和它们潜在相互作用的复杂性阻碍了对有效治疗靶点的机制理解。在这里，我们结合人类基底细胞癌的单细胞和空间转录组学，定义了肿瘤进展的细胞贡献者。在浸润性龛位中，肿瘤细胞表现出集体迁移表型，其特征是细胞-细胞连接复合物的表达。在物理临近处，我们鉴定出具有细胞外基质重塑特征的癌相关成纤维细胞。肿瘤细胞强烈表达细胞因子激活素 A，并且在相邻的癌相关成纤维细胞亚群中发现了激活素 A 诱导的基因特征增加。总之，我们的数据确定了有助于基底细胞癌浸润性龛位空间组织的细胞群体及其转录重编程。它们还证明了整合空间和单细胞多组学来破译癌症特异性浸润特性和开发靶向疗法的强大功能。
