Visualization of stem cell activity in pancreatic cancer expansion by direct lineage tracing with live imaging

Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Although rigorous efforts identified the presence of ‘cancer stem cells (CSCs)’ in PDAC and molecular markers for them, cell dynamics vivo have not been clearly demonstrated. Here we focused on Doublecortin-like kinase 1 (Dclk1), known as CSC marker PDAC. Using genetic lineage tracing with dual-recombinase system live imaging, showed that Dclk1 + tumor continuously provided progeny within pancreatic intraepithelial neoplasia, primary metastatic PDAC, PDAC-derived spheroids vitro. Furthermore, genes associated epithelial mesenchymal transition were enriched mouse human DCLK1-high cells. Thus, direct functional evidence activity vivo, revealing essential roles expansion neoplasia all progressive stages.