The plasticity of pancreatic cells

[摘要] The pancreas is a gland with both exocrine and endocrine roles. It is both involved in digesting food and secreting the hormones that regulate blood glucose. Two important diseases related to these two components of the pancreas are pancreatic cancer and diabetes. The fundamental problem for diabetes is the deficiency of insulin-secreting β cells. One strategy to reverse the diabetic condition is to supplement patients with more β cells, either by transplantation of in vitro derived β cells or by stimulating endogenous progenitor cells to differentiate into mature β cells. In Chapter 2, I describe the study I carried out in zebrafish to lineage trace a ptf1a-expressing cell population. Insights we obtained from studying the endogenous pancreatic developmental mechanism will hopefully benefit us in deriving more efficient method to generate β cells in the future. In Chapter 3, I present the work on characterizing an Aldefluor positive, Sca-1 positive progenitor population in the adult mouse pancreas. The motivation of this study is that this progenitor population may represent a cellular source that could be readily exploited to generate new β cells. Another important disease of the pancreas is pancreatic cancer. Rigorous lineage tracing studies have shown that acinar cells are the cellular origins for pancreatic ductal adenocarcinoma, the predominant type of pancreatic cancer. In Chapter 4, I depict the work on the role of Dicer, the master regulator of miRNA pathway, in the pancreatic acinar tissue homeostasis and during the initiation of pancreatic cancer. In Chapter 5, I outline our efforts in characterization the role of one particular miRNA cluster, mir-216b-217, during the processes of pancreatic acinar cell-fate maintenance and pathophysiological changes of pancreatic cancer. Together, my thesis work provides new insight into the plasticity of pancreatic cells and provide the scientific field with novel tools for further investigating the mechanisms of pancreatic development, diabetes and pancreatic cancer. It is hoped my efforts will also point to potential directions to derive clinical therapies.

[发布机构] Johns Hopkins University

[效力级别] development

[关键词] pancreas;development;adult progenitor cells;pancreatic cancer;zebrafish;mouse;ptf1a;Aldefluor;Sca-1;Dicer;miR-217;Biology