The DOI matches its Crossref record; 33 of the 33 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Generalized lacZ expression with the ROSA26 Cre reporter strain
Soriano, P. (1999) · Nature Genetics · doi:10.1038/5007 · Cited by 5,237
Adult pancreatic β-cells are formed by self-duplication rather than stem-cell differentiation
Dor, Y., Brown, J., Martinez, O. I., & Melton, D. A. (2004) · Nature · doi:10.1038/nature02520 · Cited by 2,219
Gu, G., Dubauskaite, J., & Melton, D. A. (2002) · Development · doi:10.1242/dev.129.10.2447 · Cited by 1,518
Xu, G., Stoffers, D. A., Habener, J. F., & Bonner-Weir, S. (1999) · Diabetes · doi:10.2337/diabetes.48.12.2270 · Cited by 1,209
Self-citationFive stages of evolving beta-cell dysfunction during progression to diabetes
Weir, G. C., & Bonner-Weir, S. (2004) · Diabetes · doi:10.2337/diabetes.53.suppl_3.s16 · Cited by 1,126
Indra, A. K., Warot, X. M., Brocard, J., Bornert, J., Xiao, J. H., Chambon, P., & METZGER, D. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.22.4324 · Cited by 758
β cell replication is the primary mechanism for maintaining postnatal β cell mass
Georgia, S. K., & Bhushan, A. (2004) · Journal of Clinical Investigation · doi:10.1172/jci22098 · Cited by 510
Cell lineage ablation in transgenic mice by cell-specific expression of a toxin gene
Palmiter, R. D., Behringer, R. R., Quaife, C. J., Maxwell, F., Maxwell, I. H., & Brinster, R. L. (1987) · Cell · doi:10.1016/0092-8674(87)90497-1 · Cited by 474
Very Slow Turnover of β-Cells in Aged Adult Mice
Teta, M., Long, S. Y., Wartschow, L. M., Rankin, M. M., & Kushner, J. A. (2005) · Diabetes · doi:10.2337/diabetes.54.9.2557 · Cited by 465
Molecular basis of transdifferentiation of pancreas to liver
Shen, C., Slack, J. M. W., & Tosh, D. (2000) · Nature Cell Biology · doi:10.1038/35046522 · Cited by 403
Recapitulation of elements of embryonic development in adult mouse pancreatic regeneration.
Jensen, J., Cameron, E., Garay, M., Starkey, T. W., Gianani, R., & Jensen, J. (2005) · Gastroenterology · doi:10.1053/j.gastro.2004.12.008 · Cited by 361
Means, A. L., Meszoely, I. M., Suzuki, K., Miyamoto, Y., Rustgi, A. K., Coffey, R. J., Wright, C. V. E., Stoffers, D. A., & Leach, S. D. (2005) · Development · doi:10.1242/dev.01925 · Cited by 344
Self-citationZhou, J., Wang, X., Piñeyro, M. A., & Egan, J. (1999) · Diabetes · doi:10.2337/diabetes.48.12.2358 · Cited by 319
Sapir, T., Shternhall-Ron, K., Meivar‐Levy, I., Blumenfeld, T., Cohen, H., Skutelsky, E., Eventov‐Friedman, S., Barshack, I., Goldberg, I., Pri‐Chen, S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0405277102 · Cited by 297
Mashima, H., Ohnishi, H., Wakabayashi, K., Mine, T., Miyagawa, J., Hanafusa, T., Seno, M., Yamada, H., & Kojima, I. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118591 · Cited by 278
Minami, K., Okuno, M., Miyawaki, K., Okumachi, A., Ishizaki, K., Oyama, K., Kawaguchi, M., Ishizuka, N., Iwanaga, T., & Seino, S. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0507567102 · Cited by 261
Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro
Rooman, I., Heremans, Y., Heimberg, H., & Bouwens, L. (2000) · Diabetologia · doi:10.1007/s001250051468 · Cited by 192
Miyatsuka, T., Kaneto, H., Shiraiwa, T., Matsuoka, T., Yamamoto, K., Kato, K., Nakamura, Y., Akira, S., Takeda, K., Kajimoto, Y., et al. (2006) · Genes & Development · doi:10.1101/gad.1412806 · Cited by 177
Role of Endogenous Glucagon-Like Peptide-1 in Islet Regeneration After Partial Pancreatectomy
León, D. D. D., Deng, S., Madani, R., Ahima, R. S., Drucker, D. J., & Stoffers, D. A. (2003) · Diabetes · doi:10.2337/diabetes.52.2.365 · Cited by 173
Self-citationNeural crest expression of Cre recombinase directed by the proximal Pax3 promoter in transgenic mice
Li, J., Chen, F., & Epstein, J. A. (2000) · genesis · doi:10.1002/(sici)1526-968x(200002)26:2 · Cited by 158
Formation of insulin-producing cells from pancreatic acinar AR42J cells by hepatocyte growth factor
Mashima, H., Shibata, H., Mine, T., & Kojima, I. (1996) · Endocrinology · doi:10.1210/endo.137.9.8756573 · Cited by 153
Pancreatic Islet Transplantation
Naftanel, M. A., & Harlan, D. M. (2004) · PLoS Medicine · doi:10.1371/journal.pmed.0010058 · Cited by 120
Hammer, R. E., Swift, G. H., Ornitz, D. M., Quaife, C. J., Palmiter, R. D., Brinster, R. L., & MacDonald, R. J. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.8.2956 · Cited by 108
Exocrine cell transdifferentiation in dexamethasone-treated rat pancreas
Lardon, J., Huyens, N., Rooman, I., & Bouwens, L. (2004) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-003-0930-z · Cited by 97
Advances in pancreatic islet transplantation in humans
Nanji, S. A., & Shapiro, A. M. J. (2005) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2005.00476.x · Cited by 93
Gmyr, V., Kerr-Conte, J. A., Belaich, S., Vandewalle, B., Leteurtre, E., Vantyghem, M., Lecomte-Houcke, M., Proye, C. A. G., Lefèbvre, J., & Pattou, F. N. (2000) · Diabetes · doi:10.2337/diabetes.49.10.1671 · Cited by 89
Metabolic adaptations to chronic glucose infusion in rats
Topp, B. G., McArthur, M. D., & Finegood, D. T. (2004) · Diabetologia · doi:10.1007/s00125-004-1493-5 · Cited by 69
Scoggins, C. R., Meszoely, I. M., Wada, M., Means, A. L., Yang, L., & Leach, S. D. (2000) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2000.279.4.g827 · Cited by 61
Self-citationHeller, R. S., Stoffers, D. A., Bock, T. G., Svenstrup, K., Jensen, J. N., Horn, T. D., Miller, C. P., Habener, J. F., Madsen, O. D., & Serup, P. (2001) · Diabetes · doi:10.2337/diabetes.50.7.1553 · Cited by 58
Self-citationEndocrine/Exocrine Intermediate Cells in Streptozotocin-Treated Ins-IFN-γ Transgenic Mice
Gu, D., Arnush, M., & Sarvetnick, N. (1997) · Pancreas · doi:10.1097/00006676-199710000-00005 · Cited by 52
Hammer, R. E., Swift, G. H., Ornitz, D. M., et al. (1987) · Molecular and Cellular Biology · doi:10.1128/mcb.7.8.2956-2967.1987 · Cited by 37
Lectin as a marker for staining and purification of embryonic pancreatic epithelium
Kobayashi, H., Spilde, T. L., Li, Z., Marosky, J. K., Bhatia, A. M., Hembree, M. J., Prasadan, K. L., Preuett, B. L., & Gittes, G. K. (2002) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(02)00278-4 · Cited by 32
No Stem Cell Is an Islet (Yet)
Stainier, D. Y. R. (2006) · New England Journal of Medicine · doi:10.1056/nejmcibr055048 · Cited by 16
Research works printed but not linked: 1
- 10.1172/JCI200422098 · DOI
Cited by
Sorted by citations
Pancreatic cancer: Advances and challenges
Halbrook, C. J., Lyssiotis, C. A., Pasca di Magliano, M., & Maitra, A. (2023) · Cell · doi:10.1016/j.cell.2023.02.014 · Cited by 1,321
Furuyama, K., Kawaguchi, Y., Akiyama, H., Horiguchi, M., Kodama, S., Kuhara, T., Hosokawa, S., Elbahrawy, A., Soeda, T., Koizumi, M., et al. (2010) · Nature Genetics · doi:10.1038/ng.722 · Cited by 841
p53 status determines the role of autophagy in pancreatic tumour development
Rosenfeldt, M. T., O’Prey, J., Morton, J. P., Nixon, C., MacKay, G., Mrowinska, A., Au, A., Rai, T. S., Zheng, L., Ridgway, R., et al. (2013) · Nature · doi:10.1038/nature12865 · Cited by 713
Kopp, J. L., von Figura, G., Mayes, E., Liu, F.-F., Dubois, C. L., Morris, J. P., Pan, F. C., Akiyama, H., Wright, C. V. E., Jensen, K., et al. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.10.025 · Cited by 697
Pancreas organogenesis: From bud to plexus to gland
Pan, F. C., & Wright, C. V. E. (2011) · Developmental Dynamics · doi:10.1002/dvdy.22584 · Cited by 647
Metadata
- 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 › Endocrinology, Diabetes and Metabolism › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review