Neurog3 misexpression unravels mouse pancreatic ductal cell plasticity

作者：Vieira Andhira; Vergoni Bastien; Courtney Monica; Druelle Noemie; Gjernes Elisabet; Hadzic Biljana; Avolio Fabio; Napolitano Tiziana; Sanz Sergi Navarro; Mansouri Ahmed; Collombat Patrick^*

来源：PLos One, 2018, 13(8): e0201536.

DOI：10.1371/journal.pone.0201536

In the context of type 1 diabetes research and the development of insulin-producing beta-cell replacement strategies, whether pancreatic ductal cells retain their developmental capability to adopt an endocrine cell identity remains debated, most likely due to the diversity of models employed to induce pancreatic regeneration. In this work, rather than injuring the pancreas, we developed a mouse model allowing the inducible misexpression of the proendocrine gene Neurog3 in ductal cells in vivo. These animals developed a progressive islet hypertrophy attributed to a proportional increase in all endocrine cell populations. Lineage tracing experiments indicated a continuous neo-generation of endocrine cells exhibiting a ductal ontogeny. Interestingly, the resulting supplementary beta-like cells were found to be functional. Based on these findings, we suggest that ductal cells could represent a renewable source of new beta-like cells and that strategies aiming at controlling the expression of Neurog3, or of its molecular targets/co-factors, may pave new avenues for the improved treatments of diabetes.

• 出版日期2018-8-9