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

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Item Type:Article
Title:Tracing tumorigenesis in a solid tumor model at single-cell resolution
Creators Name:Praktiknjo, S.D. and Obermayer, B. and Zhu, Q. and Fang, L. and Liu, H. and Quinn, H. and Stoeckius, M. and Kocks, C. and Birchmeier, W. and Rajewsky, N.
Abstract: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.
Keywords:Carcinogenesis, Squamous Cell Carcinoma, Cell Differentiation, Cell Lineage, Neoplastic Cell Transformation, Epithelial-Mesenchymal Transition, Gene Expression Profiling, Inbred C57BL Mice, Transgenic Mice, Neoplastic Stem Cells, Messenger RNA, RNA-Seq, Salivary Gland Neoplasms, Single-Cell Analysis, Tumor Microenvironment, Animals, Mice
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:991
Date:20 February 2020
Official Publication:https://doi.org/10.1038/s41467-020-14777-0
PubMed:View item in PubMed

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