Centroacinar Cells Are Progenitors That Contribute to Endocrine Pancreas Regeneration.

Autor:	Delaspre F; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD., Beer RL; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD., Rovira M; Genomic Programming of Beta-Cells Laboratory, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain., Huang W; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD., Wang G; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD., Gee S; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD., Vitery Mdel C; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD., Wheelan SJ; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD Department of Oncology, Johns Hopkins University, Baltimore, MD., Parsons MJ; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD Department of Surgery, Johns Hopkins University, Baltimore, MD mparson3@jhmi.edu.
Jazyk:	angličtina
Zdroj:	Diabetes [Diabetes] 2015 Oct; Vol. 64 (10), pp. 3499-509. Date of Electronic Publication: 2015 Jul 07.
DOI:	10.2337/db15-0153
Abstrakt:	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. (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
Databáze:	MEDLINE
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