Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regeneration
Open accessAbstract
It has been suggested that pancreatic acinar cells can serve as progenitors for pancreatic islets, a concept with substantial implications for therapeutic efforts to increase insulin-producing beta cell mass in patients with diabetes. We report what we believe to be the first in vivo lineage tracing approach to determine the plasticity potential of pancreatic acinar cells. We developed an acinar cell-specific inducible Cre recombinase transgenic mouse, which, when mated with a reporter strain and pulsed with tamoxifen, resulted in permanent and specific labeling of acinar cells and their progeny. During various time periods of observation and using several models to provoke injury, we failed to observe any chase of the labeled cells into the endocrine compartment, indicating that acinar cells do not normally transdifferentiate into islet beta cells in vivo in adult mice. In contrast, we observed a substantial role for replication of preexisting acinar cells in the regeneration of new acinar cells after partial pancreatectomy. These results indicate that mature acinar cells harbor a facultative acinar but not endocrine progenitor capacity.
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Lineage tracing studies in mice confirmed that acinar cells can repopulate damaged tissue.
“lineage tracing studies in mice confirmed that acinar cells can repopulate damaged tissue112.”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [112]
Normal β-cell growth primarily occurs by self-renewal of mature β-cells-not by replication of specialized progenitors.
“the findings of recent studies by several groups (including ours) indicate that normal β-cell growth primarily occurs by self-renewal of mature β-cells—not by replication of specialized progenitors (8–12).”
From Adaptive β-Cell Proliferation Is Severely Restricted With Advanced Age (2009) · cites this paper as [12]
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- Authors
- Desai, B. M., Oliver-Krasinski, J., De Leon, D. D., Farzad, C., Hong, N., Leach, S. D., & Stoffers, D. A.
- Affiliations
- University of Pennsylvania (US)
- Johns Hopkins University (US)
- Corresponding author
- Stoffers, Doris A.
- Venue
- Journal of Clinical Investigation
- Published
- 2007-04-02
- Volume
- 117
- Issue
- 4
- Pages
- 971-977
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1838936
- OpenAlex
- W1967081779
- Cited by
- 303
- References
- 32
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 7 · 2023: 10 · 2022: 6 · 2021: 19 · 2020: 17 · 2019: 12 · 2018: 12 · 2017: 8 · 2016: 21 · 2015: 17 · 2014: 20 · 2013: 23 · 2012: 16
- FWCI
- 25.96
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Diabetes Association
- National Institutes of Health (5f31hl071273-02)
- National Heart, Lung, and Blood Institute (5F31HL071273, F31 HL071273)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK56211, R01DK056211, DK-50306, P01-DK49210, DK61215, P01DK049210, R01DK061215, P30DK50306, P30DK019525, P30DK050306)
- Topics
- Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Health Sciences › Medicine › Surgery › Pancreatitis Pathology and Treatment
- Keywords
- pancreatic acinar cells, beta cell regeneration, islet regeneration, transdifferentiation, lineage tracing, inducible Cre recombinase, partial pancreatectomy, pancreatic progenitor cells, cellular plasticity, diabetes mellitus
- MeSH terms
- Animals, Digestive System Physiological Phenomena, Mice, Transgenic, Organ Specificity, Pancreas, Regeneration, Tamoxifen, Integrases, Reverse Transcriptase Polymerase Chain Reaction, Insulin-Secreting Cells, Mice, Rats
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