Single cell transcriptomic analysis of epithelial and mesenchymal tumour cells

Pancreatic ductal adenocarcinoma (PDAC) exhibits pronounced heterogeneity with multiple subtypes along the epithelial-to-mesenchymal axis co-existing simultaneously in tumours. Here, we used previously characterized epithelial and mesenchymal primary PDAC cell lines from a KC mouse model (2D bulk cell populations) (Mueller et al. 2018) and perform single-cell RNA sequencing to determine how heterogeneous these bulk tumour cells are and if they express different levels of epithelial-mesenchymal transition/plasticity signatures. In our study, we identified that the same bulk population of tumour cells can give rise to various morphological and transcriptionally distinct organoid phenotypes. Therefore, we examined if specific preexisting subclusters within each line (subtype specific) were already enriched for distinct phenotype signatures from our organoid phenotype landscape.