title: Preexisting pancreatic acinar cells contribute to acinar cell, but not islet beta cell, regeneration.
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 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.
authors.affiliation: Division of Endocrinology, Diabetes, and Metabolism and Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Biva M
authors.initials: BM
authors.lastname: Desai
authors.forename: Jennifer
authors.initials: J
authors.lastname: Oliver-Krasinski
authors.forename: Diva D
authors.initials: DD
authors.lastname: De Leon
authors.forename: Cyrus
authors.initials: C
authors.lastname: Farzad
authors.forename: Nankang
authors.initials: N
authors.lastname: Hong
authors.forename: Steven D
authors.initials: SD
authors.lastname: Leach
authors.forename: Doris A
authors.initials: DA
authors.lastname: Stoffers
mesh_terms: D000818:Animals; D004068:Digestive System Physiological Phenomena; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D019426:Integrases / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D012038:Regeneration; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D013629:Tamoxifen; C045073:Cre recombinase; D019426:Integrases