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

Judith Magenheim, Miguel Angel Maestro, Nadav Sharon, Pedro L. Herrera, L. Charles Murtaugh, Janel Kopp, Maike Sander, Guoqiang Gu, Douglas A. Melton, Jorge Ferrer*, Yuval Dor*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


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.

Original languageAmerican English
Pages (from-to)488-497.e3
JournalCell Stem Cell
Issue number4
StatePublished - 6 Apr 2023

Bibliographical note

Funding Information:
We thank Dana Tzfati and Danny Ben-Zvi for critical comments on this manuscript. This research was supported by Ministerio de Ciencia e Innovación to J.F. (PID2021-122522OB-I00 and RTI2018-095666-B-I00 ). Work in CRG was supported by the CERCA Program (Generalitat de Catalunya) and Centro de Excelencia Severo Ochoa ( CEX2020-001049-S ). Y.D. holds the Walter and Greta Stiel Chair and Research grant in heart studies. M.S. is supported by NIH grants DK078803 and DK068471 .

Publisher Copyright:
© 2023 Elsevier Inc.


  • beta cell regeneration
  • beta cells
  • delta cells
  • ducts
  • lineage tracing
  • neogenesis
  • pancreas
  • progenitor cells
  • stem cells


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