Recently, Zhou Bin, Center of Excellence in Molecular Cell Sciences (Institute of Biochemistry and Cell Biology), Chinese Academy of Sciences, published their research results in Cell Discovery with Use of a dual genetic system to decipher exocrine cell fate conversions in the adult pancreas. This study developed a new dual-homologous recombinase-mediated lineage tracing technique that can simultaneously trace ductal cells and acinar cells of the pancreas, which revealed that pancreatic ductal cells and acinar cells can undergo cell fate transitions under specific conditions. This study provides a certain theoretical basis for the clinical treatment of pancreatitis and other related diseases.
The pancreas is the second largest gland in the body after the liver, in which the exocrine part constitutes the vast majority of the pancreas, mainly composed of acinar cells and ductal cells. Acinar cells can produce and release a large number of digestive enzymes, including amylase, lipase, etc. These digestive enzymes are transported to the duodenum through the pancreatic duct and play an important role in the digestive process of the body. In the pancreas, whether exocrine ductal cells and acinar cells can undergo lineage transition under physiopathological conditions remains somewhat controversial. Traditional multiple genetic tracing work based on Cre-loxP has different results for the cell lineage transition in the exocrine part of the pancreas. Uncovering pancreatic ductal cell and acinar cell fate transition can provide help and basis for the prevention and targeted treatment of pancreas-related diseases.
To systematically investigate cell lineage fate shift in the pancreatic exocrine region, a novel dual homologous lineage tracing technique that can simultaneously trace pancreatic ductal cells and acinar cells. We found that Tnni 3-Dre and orthogonal site-specific double homologous recombination system crossover reporter mouse IR 1 could specifically label acinar cells in the pancreatic exocrine region, but basically not other cell types, and avoid "non-specific labeling" of acinar cells in CK19-CreER mice by labeling pancreatic ductal cells and acinar cells with two different permanent genetic reporters: zsGreen and tdTomato.
Using this system, the researchers found that in homeostasis and pancreatic resection, pancreatic ductal cells and acinar cells mainly derived from self-replication, and in the pancreatic ductal ligation and rain induced pancreatitis model, part of the pancreatic acinar cells into tubular structure, and no longer express acinar cell markers, cell fate into ductal cells. However, after using diphtheria toxin-mediated removal of most pancreatic acinar cells, pancreatic ductal cells can be seen to contribute part of the acinar cells. Using single-cell sequencing technology, we found that ductal cells undergo an immature acinar cell, indicating that pancreatic ductal cells also have the potential to transdifferentiate into acinar cells. This research work provides new research tools and ideas for the deep exploration of the pathogenesis of pancreatitis and other related diseases and the research of disease treatment.
