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

Item Type:	Article
Title:	Matters arising: Insufficient evidence that pancreatic β cells are derived from adult ductal Neurog3-expressing progenitors
Creators Name:	Magenheim, J. and Maestro, M.A. and Sharon, N. and Herrera, P.L. and Murtaugh, L.C. and Kopp, J. and Sander, M. and Gu, G. and Melton, D.A. and 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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