The integration of ST and imaging enables automated cell type annotation of ST spots at a single-cell resolution, enabling spot selection and deconvolution for unique cellular components of the tumor microenvironment (TME). We further developed novel multi-omics analysis methods for threefold integration of imaging, ST, and scRNA-seq data to analyze the premalignant microenvironment. We developed a new experimental pipeline for FFPE ST analysis of PanINs that preserves clinical specimens for diagnosis. Pancreatic intraepithelial neoplasia (PanIN) is a premalignant lesion with potential to develop into PDAC, but the formalin-fixed and paraffin-embedded (FFPE) specimens required for PanIN diagnosis preclude scRNA-seq profiling. Nonetheless, the evolutionary processes yielding that microenvironment remain unknown. Previous single-cell RNA-sequencing (scRNA-seq) studies of pancreatic ductal adenocarcinoma (PDAC) have revealed a complex immunosuppressive environment characterized by numerous cancer associated fibroblasts (CAFs) subtypes that contributes to poor outcomes.
Spatial transcriptomics (ST) is a powerful new approach to characterize the cellular and molecular architecture of the tumor microenvironment.
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