Matters arising: Insufficient evidence that pancreatic β cells are derived from adult ductal Neurog3-expressing progenitors

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Item Type:	Article
Title:	Matters arising: Insufficient evidence that pancreatic β cells are derived from adult ductal Neurog3-expressing progenitors
Creators Name:	Magenheim, J., Maestro, M.A., Sharon, N., Herrera, P.L., Murtaugh, L.C., Kopp, J., Sander, M., Gu, G., Melton, D.A., Ferrer, J. and Dor, Y.
Abstract:	Understanding the origin of pancreatic β cells has profound implications for regenerative therapies in diabetes. For over a century, it was widely held that adult pancreatic duct cells act as endocrine progenitors, but lineage-tracing experiments challenged this dogma. Gribben et al. recently used two existing lineage-tracing models and single-cell RNA sequencing to conclude that adult pancreatic ducts contain endocrine progenitors that differentiate to insulin-expressing β cells at a physiologically important rate. We now offer an alternative interpretation of these experiments. Our data indicate that the two Cre lines that were used directly label adult islet somatostatin-producing ∂ cells, which precludes their use to assess whether β cells originate from duct cells. Furthermore, many labeled ∂ cells, which have an elongated neuron-like shape, were likely misclassified as β cells because insulin-somatostatin coimmunolocalizations were not used. We conclude that most evidence so far indicates that endocrine and exocrine lineage borders are rarely crossed in the adult pancreas.
Keywords:	Pancreas, Beta Cells, Delta Cells, Stem Cells, Progenitor Cells, Ducts, Neogenesis, NEUROG3, Lineage Tracing, Beta Cell Regeneration
Source:	Cell Stem Cell
ISSN:	1934-5909
Publisher:	Cell Press
Volume:	30
Number:	4
Page Range:	488-497
Date:	6 April 2023
Official Publication:	https://doi.org/10.1016/j.stem.2023.03.003
PubMed:	View item in PubMed

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