Tracing tumorigenesis in a solid tumor model at single-cell resolution

• Published in: Nature communications Vol. 11; no. 1; pp. 991 - 12
• Main Authors: Praktiknjo, Samantha D., Obermayer, Benedikt, Zhu, Qionghua, Fang, Liang, Liu, Haiyue, Quinn, Hazel, Stoeckius, Marlon, Kocks, Christine, Birchmeier, Walter, Rajewsky, Nikolaus
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.02.2020; Nature Publishing Group; Nature Portfolio
• Subjects: 14/63; 38/62; 49/1; 49/39; 49/91; 631/114; 631/337/2019; 631/337/475; 631/67/71; 64/60; 692/420/755; 82/47; 82/51; 96/31; Animals; Basal cells; Cancer; Carcinogenesis - genetics; Carcinogenesis - immunology; Carcinogenesis - pathology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Cell differentiation; Cell Differentiation - genetics; Cell Differentiation - immunology; Cell Lineage - genetics; Cell Lineage - immunology; Cell Transformation, Neoplastic - genetics; Cell Transformation, Neoplastic - immunology; Cell Transformation, Neoplastic - pathology; Epithelial-Mesenchymal Transition - genetics; Epithelial-Mesenchymal Transition - immunology; Epitopes; Gene expression; Gene Expression Profiling; Humanities and Social Sciences; Mesenchyme; Metastases; Mice; Mice, Inbred C57BL; Mice, Transgenic; multidisciplinary; Neoplastic Stem Cells - classification; Neoplastic Stem Cells - immunology; Neoplastic Stem Cells - pathology; RNA, Messenger - genetics; RNA-Seq; Salivary gland; Salivary Gland Neoplasms - genetics; Salivary Gland Neoplasms - immunology; Salivary Gland Neoplasms - pathology; Salivary glands; Science; Science (multidisciplinary); Single-Cell Analysis; Solid tumors; Squamous cell carcinoma; Stem cells; Subpopulations; Tumor Microenvironment - genetics; Tumor Microenvironment - immunology; Tumorigenesis; Tumors; Wnt protein
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-14777-0

Characterizing the complex composition of solid tumors is fundamental for understanding tumor initiation, progression and metastasis. While patient-derived samples provide valuable insight, they are heterogeneous on multiple molecular levels, and often originate from advanced tumor stages. Here, we use single-cell transcriptome and epitope profiling together with pathway and lineage analyses to study tumorigenesis from a developmental perspective in a mouse model of salivary gland squamous cell carcinoma. We provide a comprehensive cell atlas and characterize tumor-specific cells. We find that these cells are connected along a reproducible developmental trajectory: initiated in basal cells exhibiting an epithelial-to-mesenchymal transition signature, tumorigenesis proceeds through Wnt-differential cancer stem cell-like subpopulations before differentiating into luminal-like cells. Our work provides unbiased insights into tumor-specific cellular identities in a whole tissue environment, and emphasizes the power of using defined genetic model systems. Understanding tumour development at a granular level is a challenge in solid tumours. Here, the authors provide a cell atlas across tumour development in a genetic model of salivary gland squamous cell carcinoma using single-cell transcriptome and epitope profiling.