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


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


  • Nature Communications


  • Nat Commun 11 (1): 991


  • 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.