Finally, to understand conserved principles in stem cell activation of quiescent organs, we have applied the methods we pioneered for the brain, to the the exocrine pancreas, that provides a model with a much lower degree of cell type complexity and an important cancer type with high mortality and few therapeutic possibilities. To validate this model, we first addressed if the pancreas, which is currently thought to be quiescent, contains a progenitor-like subpopulation among pancreatic acinar cells that account for 80% of pancreatic cells and are the origin of pancreatic ductal adenocarcinoma (PDAC). Exploiting the power of our single-cell technologies including lineage tracing and single-cell transcriptomics allowed us to identify a specialized subset of acinar cells with long-term renewal. In addition, we identified a novel population of terminally differentiated post-mitotic binuclear cells in the human pancreas (Wollny et al., 2016). Our future work in this system will focus in understanding how these newly identified pancreatic adult stem cells contribute to tumorigenesis in animal model of pancreatic cancer.