Insights from integrating single cell gene expression and spatial profiling of pancreatic tumors
Researchers led by Ludwig MIT Co-director Tyler Jacks and alum Aviv Regev constructed a high-resolution molecular landscape of the cellular subtypes and spatial communities that compose pancreatic ductal adenocarcinoma tumors using single-nucleus RNA sequencing and whole-transcriptome digital spatial profiling on specimens that either received neoadjuvant therapy or were treatment naive. They reported in Nature Genetics in July their discovery of recurrent gene expression programs across malignant cells and fibroblasts, including what they describe as a neural-like progenitor malignant cell program associated with poor prognosis that rose in prominence following chemotherapy and radiotherapy. Their integration of spatial and cellular profiles uncovered three multicellular communities that had distinct contributions from subtypes of fibroblasts, cancer cells and immune cells. They suggest their refined molecular and cellular taxonomy offers a framework for patient stratification in clinical trials and could inform the targeting of specific cellular states and multicellular interactions.