Pancreatic ductal adenocarcinoma (PDAC) is projected to be the second leading cause of cancer mortality by 2030. Bulk transcriptomic analyses have distinguished ‘classical’ from ‘basal-like’ tumors with more aggressive clinical behaviour. Here, the researchers derive PDAC organoids from 18 primary tumors and two matched liver metastases, and show that ‘classical’ and ‘basal-like’ cells coexist in individual organoids. By single-cell transcriptome analysis of PDAC organoids and primary PDAC, they identify distinct tumor cell states shared across patients. In an imaging-based drug screen, expression of ‘classical’ subtype genes correlates with better drug response. These results thus uncover a functional hierarchy of PDAC cell states linked to transcriptional tumor subtypes and support the use of PDAC organoids as a clinically relevant model for in vitro studies of tumor heterogeneity.
Single-cell analysis of patient-derived PDAC organoids reveals cell state heterogeneity and a conserved developmental hierarchy
Roland Eils(1), Christian Conrad(1), Oliver Strobel(2)
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