|ZFIN ID: ZDB-PUB-150711-15|
Centroacinar cells are progenitors that contribute to endocrine pancreas regeneration
Delaspre, F., Beer, R.L., Rovira, M., Huang, W., Wang, G., Gee, S., Vitery, M.D., Wheelan, S.J., Parsons, M.J.
|Source:||Diabetes 64(10): 3499-509 (Journal)|
|Registered Authors:||Beer, Rebecca, Delaspre, Fabien, Huang, Wei, Parsons, Michael, Wang, Guangliang (Johnny)|
|PubMed:||26153247 Full text @ Diabetes|
Delaspre, F., Beer, R.L., Rovira, M., Huang, W., Wang, G., Gee, S., Vitery, M.D., Wheelan, S.J., Parsons, M.J. (2015) Centroacinar cells are progenitors that contribute to endocrine pancreas regeneration. Diabetes. 64(10):3499-509.
ABSTRACTDiabetes 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 utilize 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 following β-cell ablation or partial pancreatectomy. We concluded that CACs and their larval predecessors are the same cell type and represent an opportune model by which 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.