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Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regeneration
Biva M. Desai, Jennifer Oliver-Krasinski, Diva D. De Leon, Cyrus Farzad, Nankang Hong, Steven D. Leach, Doris A. Stoffers
Biva M. Desai, Jennifer Oliver-Krasinski, Diva D. De Leon, Cyrus Farzad, Nankang Hong, Steven D. Leach, Doris A. Stoffers
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Research Article

Preexisting pancreatic acinar cells contribute to acinar cell, but not islet β cell, regeneration

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Abstract

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 β 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 β 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.

Authors

Biva M. Desai, Jennifer Oliver-Krasinski, Diva D. De Leon, Cyrus Farzad, Nankang Hong, Steven D. Leach, Doris A. Stoffers

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Figure 1

CreERT2 expression is restricted to the pancreas of ElastaseCreERT2 transgenic mice.

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CreERT2 expression is restricted to the pancreas of ElastaseCreERT2 tran...
(A) Schematic depiction of the elastase CreERT2 transgene. The transgene contains the 0.5-kb proximal rat elastase I promoter (Elas; gray), the rabbit β-globin intron (RBG intron; black), the coding region for CreERT2 (white), and the rabbit β-globin polyadenylation cassette (RBG PolyA; black). (B) Schematic depiction of the Rosa26r reporter locus and the effect of TAM-induced Cre recombinase activity to excise a loxP-flanked stop sequence (dashed lines), thereby allowing transcription of LacZ (i.e., β-galactosidase; arrow). (C) Tissue distribution of Cre recombinase expression, determined by RT-PCR for Cre recombinase mRNA using total RNA isolated from the designated tissues of 16-week-old transgenic mice. Panc, pancreas; Stom, stomach; SI, small intestine; LI, large intestine; Ht, heart; Lu, lung; Li, liver; Kid, kidney; Spl, spleen. (D) Time course indicating low basal Cre-mediated recombination and high inducibility by TAM administration. RT-PCR for β-galactosidase mRNA carried out using RNA isolated from pancreata of 16-week-old transgenic mice left untreatd or after 3, 7, or 10 days of TAM treatment.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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