Continuous clonal labeling reveals uniform progenitor potential in the adult exocrine pancreas

Summary The tissue dynamics that govern maintenance and regeneration of the pancreas remain largely unknown. In particular, the presence and nature of a cellular hierarchy remains a topic of debate. Previous lineage tracing strategies in the pancreas relied on specific marker genes for clonal labeling, which left other populations untested and failed to account for potential widespread phenotypical plasticity. Here we employed a tracing system that depends on replication-induced clonal marks. We found that, in homeostasis, steady acinar replacement events characterize tissue dynamics, to which all acinar cells have an equal ability to contribute. Similarly, regeneration following pancreatitis was best characterized by an acinar self-replication model because no evidence of a cellular hierarchy was detected. In particular, rapid regeneration in the pancreas was found to be driven by an accelerated rate of acinar fission-like events. These results provide a comprehensive and quantitative model of cell dynamics in the exocrine pancreas.
Graphical abstract
Highlights • All acinar cells have an equal probability to contribute to tissue renewal • All acinar cells function as bona fide progenitor cells during homeostasis • Acinar fission-like events underlie pancreas regeneration
The dynamics of tissue maintenance in the adult exocrine pancreas are largely unknown. In this study, Lodestijn et al. use a combination of experimental and computational methods to reveal that there is no hierarchy in the adult exocrine pancreas and that all cells can act as bona fide progenitors.