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.
Original language | English |
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Pages (from-to) | 488-497.e3 |
Journal | Cell Stem Cell |
Volume | 30 |
Issue number | 4 |
DOIs | |
State | Published - 6 Apr 2023 |
Bibliographical note
Publisher Copyright:© 2023 Elsevier Inc.
Keywords
- NEUROG3
- beta cell regeneration
- beta cells
- delta cells
- ducts
- lineage tracing
- neogenesis
- pancreas
- progenitor cells
- stem cells