Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA; Stanford Cancer Institute, Stanford University School of Medicine, Stanford, CA 94305, USA.
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Cell. 2020 Jul 23;182(2):497-514.e22. doi: 10.1016/j.cell.2020.05.039. Epub 2020 Jun 23.
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.
为了定义皮肤鳞状细胞癌 (cSCC) 的细胞组成和结构，我们结合了单细胞 RNA 测序、空间转录组学和一系列人类 cSCC 及匹配正常皮肤的多重离子束成像。cSCC 表现出四种肿瘤亚群，其中三种重现了正常表皮状态，还有一种独特于癌症的肿瘤特异性角蛋白细胞 (TSK) 群，定位于纤维血管龛位。单细胞和空间数据的整合将配体-受体网络映射到特定的细胞类型，揭示 TSK 细胞作为细胞间通讯的枢纽。观察到多种潜在的免疫抑制特征，包括 T 调节细胞 (Treg) 与 CD8 T 细胞在分隔的肿瘤基质中的共定位。最后，对人肿瘤异种移植物的单细胞特征分析和体内 CRISPR 筛选确定了特定肿瘤亚群丰富基因网络在肿瘤发生中的关键作用。这些数据定义了 cSCC 肿瘤和基质细胞亚群、它们相互作用的空间龛位以及它们参与癌症的通讯基因网络。
