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

Autor: Lodestijn SC; 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., van den Bosch T; 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., Nijman LE; 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., Moreno LF; 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., Schlingemann S; 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., Sheraton VM; 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., van Neerven SM; 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., Koning JJ; Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centers, De Boelelaan 1108, 1081 HV Amsterdam, the Netherlands., Vieira Braga FA; 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., Paauw NJ; Department of Molecular Cell Biology and Immunology, Amsterdam University Medical Centers, De Boelelaan 1108, 1081 HV Amsterdam, the Netherlands., Lecca MC; 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., Lenos KJ; 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., Morrissey E; MRC Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Headington, Oxford OX3 9DS, UK., Miedema DM; 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., Winton DJ; Cancer Research UK, Cambridge Institute, University of Cambridge, Robinson Way, Cambridge CB2 0RE, UK., Bijlsma MF; 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., Vermeulen L; 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.
Jazyk: angličtina
Zdroj: Cell stem cell [Cell Stem Cell] 2021 Nov 04; Vol. 28 (11), pp. 2009-2019.e4. Date of Electronic Publication: 2021 Aug 05.
DOI: 10.1016/j.stem.2021.07.004
Abstrakt: 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.
Competing Interests: Declaration of interests The authors declare no competing interests.
(Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE