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

Sophie C Lodestijn1, Tom van den Bosch1, Lisanne E Nijman1, Leandro F Moreno1, Sophie Schlingemann1, Vivek M Sheraton2, Sanne M van Neerven1, Jasper J Koning3, Felipe A Vieira Braga1, Nanne J Paauw3, Maria C Lecca1, Kristiaan J Lenos1, Edward Morrissey4, Daniël M Miedema1, Douglas J Winton5, Maarten F Bijlsma6, Louis Vermeulen7

  1. Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.
  2. Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Institute for Advanced Study, University of Amsterdam, Oude Turfmarkt 147, 1012 GC Amsterdam, the Netherlands.
  3. Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centers, De Boelelaan 1108, 1081 HV Amsterdam, the Netherlands.
  4. MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK.
  5. Cancer Research UK, Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK.
  6. Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: m.f.bijlsma@amsterdamumc.nl.
  7. Laboratory for Experimental Oncology and Radiobiology, Center for Experimental and Molecular Medicine, Cancer Center Amsterdam and Amsterdam Gastroenterology Endocrinology and Metabolism, Amsterdam University Medical Centers, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands; Oncode Institute, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands. Electronic address: l.vermeulen@amsterdamumc.nl.

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.

Presented By Maarten F Bijlsma

Cell & Developmental BioNicholas Liao2021-11 (Nov)