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

Sophie C. Lodestijn, Tom van den Bosch, Lisanne E. Nijman, Leandro F. Moreno, Sophie Schlingemann, Vivek M. Sheraton, Sanne M. van Neerven, Jasper J. Koning, Felipe A. Vieira Braga, Nanne J. Paauw, Maria C. Lecca, Kristiaan J. Lenos, Edward Morrissey, Daniël M. Miedema, Douglas J. Winton, Maarten F. Bijlsma, Louis Vermeulen, E. Morissey

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Abstract

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.
Original languageEnglish
Pages (from-to)2009-2019.e4
Number of pages15
JournalCell Stem Cell
Volume28
Issue number11
Early online date30 Jul 2021
DOIs
Publication statusPublished - 4 Nov 2021

Keywords

  • lineage tracing
  • pancreas
  • progenitor cells
  • stem cell
  • stochastic model

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