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Systematic comparison of pancreatic ductal adenocarcinoma models identifies a conserved highly plastic basal cell state

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) portends a dire prognosis. Intra-tumoral heterogeneity and cellular plasticity have emerged as hallmarks of cancer, including PDAC. Yet, our understanding of the mechanisms underpinning cellular diversity in PDAC remains limited. Here, we investigate cellular heterogeneity of PDAC cancer cells across a range of in vitro and in vivo growth conditions using single-cell genomics. We find heterogeneity contracts significantly in 2D and 3D cell culture models but becomes restored upon orthotopic transplantation. Orthotopic transplants reproducibly acquire cell states identified in autochthonous PDAC tumors, including a basal state exhibiting co-expression and co-accessibility of epithelial and mesenchymal genes. Using linage-tracing combined with single-cell transcriptomics, we demonstrate basal cells display high plasticity in situ. This work defines the impact of cellular growth conditions on phenotypic diversity and uncovers a highly plastic cell state with the capacity to facilitate state transitions and promote intra-tumoral heterogeneity in PDAC.

ORGANISM(S): Mus musculus

PROVIDER: GSE209599 | GEO | 2022/07/25

REPOSITORIES: GEO

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