Stem-cell states converge in multi-stage cutaneous squamous cell carcinoma development [RNA-seq]

Stem cells play a critical role in cancer development by contributing to cell heterogeneity, lineage plasticity, and drug resistance. We created gene expression networks from hundreds of mouse normal and tumor samples, and integrated these with lineage tracing and single-cell RNA-seq, to identify convergence of cell states in pre-malignant tumor cells expressing markers of lineage plasticity and drug resistance. Two of these cell states representing multilineage plasticity or proliferation were inversely correlated, suggesting a mutually exclusive relationship. Treatment of carcinomas in vivo with chemotherapy repressed the proliferative state and activated multilineage plasticity, while inhibition of differentiation repressed plasticity and potentiated responses to cell-cycle inhibitors. Manipulation of this cell state transition point may provide a rich source of potential combinatorial targets for cancer therapy. These RNAseq data encompass bulk data used to treat cancer cell lines with a Pp2a inhibitor. To investigate the transcriptomic effect of inhibiting Pp2a with LB100 in two murine squamous cell cancer cell lines, CCK85 and CCK168, we grew 3 biological replicates of each cell line treated with either LB100 or control vehicle. We then performed gene expression profiling analysis using data obtained from RNA-seq.