Analysis of an engineered organoid model of pancreatic cancer identifies hypoxia as a contributing factor in determining transcriptional subtypes.

ABSTRACT: Pancreatic ductal adenocarcinoma (PDAC) is a high-mortality cancer characterized by its aggressive, treatment-resistant phenotype and a complex tumour microenvironment (TME) featuring significant hypoxia. Bulk transcriptomic analysis has identified the "classical" and "basal-like" transcriptional subtypes which have prognostic value; however, it is not well-established how microenvironmental heterogeneity contributes to these transcriptional signatures. Here, we exploited the TRACER platform to perform single cell transcriptome analysis of organoids at specific spatial locations to explore the effect of oxygen and other cell-generated microenvironmental gradients on organoid heterogeneity. We found that the microenvironmental gradients present in TRACER significantly impact the distributio

SUBMITTER: Landon-Brace N 

PROVIDER: S-EPMC12223171 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature