title: Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.
abstract: Diabetes is associated with a paucity of insulin-producing β-cells. With the goal of finding therapeutic routes to treat diabetes, we aim to find molecular and cellular mechanisms involved in β-cell neogenesis and regeneration. To facilitate discovery of such mechanisms, we use a vertebrate organism where pancreatic cells readily regenerate. The larval zebrafish pancreas contains Notch-responsive progenitors that during development give rise to adult ductal, endocrine, and centroacinar cells (CACs). Adult CACs are also Notch responsive and are morphologically similar to their larval predecessors. To test our hypothesis that adult CACs are also progenitors, we took two complementary approaches: 1) We established the transcriptome for adult CACs. Using gene ontology, transgenic lines, and in situ hybridization, we found that the CAC transcriptome is enriched for progenitor markers. 2) Using lineage tracing, we demonstrated that CACs do form new endocrine cells after β-cell ablation or partial pancreatectomy. We concluded that CACs and their larval predecessors are the same cell type and represent an opportune model to study both β-cell neogenesis and β-cell regeneration. Furthermore, we show that in cftr loss-of-function mutants, there is a deficiency of larval CACs, providing a possible explanation for pancreatic complications associated with cystic fibrosis.
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Fabien
authors.initials: F
authors.lastname: Delaspre
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Beer
authors.affiliation: Genomic Programming of Beta-Cells Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
authors.forename: Meritxell
authors.initials: M
authors.lastname: Rovira
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Guangliang
authors.initials: G
authors.lastname: Wang
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Stephen
authors.initials: S
authors.lastname: Gee
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD.
authors.forename: Maria del Carmen
authors.initials: Mdel C
authors.lastname: Vitery
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD Department of Oncology, Johns Hopkins University, Baltimore, MD.
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Wheelan
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD Department of Surgery, Johns Hopkins University, Baltimore, MD mparson3@jhmi.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parsons
mesh_terms: D061354:Acinar Cells / Q000166:cytology / Q000502:physiology*; D000818:Animals; D030801:Animals, Genetically Modified; D005786:Gene Expression Regulation / Q000502:physiology*; D007515:Islets of Langerhans / Q000502:physiology*; D007814:Larva / Q000502:physiology; D010180:Pancreatectomy; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D059467:Transcriptome; D015027:Zebrafish
chemical_list: D051880:Receptors, Notch; D012313:RNA