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

Praktiknjo, S.D.; Obermayer, B.; Zhu, Q.; Fang, L.; Liu, H.; Quinn, H.; Stoeckius, M.; Kocks, C.; Birchmeier, W.; Rajewsky, N.

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., Obermayer, B., Zhu, Q., Fang, L., Liu, H., Quinn, H., Stoeckius, M., Kocks, C., 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
ISSN:	2041-1723
Publisher:	Nature Publishing Group
Volume:	11
Number:	1
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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