Journal
CELL STEM CELL
Volume 28, Issue 11, Pages 2009-+Publisher
CELL PRESS
DOI: 10.1016/j.stem.2021.07.004
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Funding
- New York Stem Cell Foundation
- KWF [UVA2014-7245]
- Maurits en Anna de Kock Stichting [2015-2]
- Worldwide Cancer Research [14-1164]
- Maag Lever Darm Stichting [MLDS-CDG 14-03]
- European Research Council [ERG-StG 638193]
- ZonMw [Vidi 016.156.308]
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The study discovered that a self-replication model of acinar cells is more suitable to describe the dynamics of the pancreas in both homeostasis and regeneration, with no evidence of a cellular hierarchy detected. Rapid regeneration in the pancreas was found to be driven by accelerated acinar fission-like events.
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.
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