Use of a dual genetic system to decipher exocrine cell fate conversions in the adult pancreas

Cell Discovery

Article

Lingjuan He¹  Ruling Shen²  Liang Lai³  Ruilin Sun³  Xiuxiu Liu⁴  Zixin Liu⁴  Zan Lv⁴  Yi Li⁴  Wenjuan Pu⁴  Ximeng Han⁴  Xiuzhen Huang⁴  Huan Zhao⁴  Yan Li⁴  Bin Zhou⁵ 

[1] School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China;Shanghai Laboratory Animal Research Center, Shanghai, China;Shanghai Model Organisms Center, Inc., Shanghai, China;State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China;State Key Laboratory of Cell Biology, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China;School of Life Science and Technology, ShanghaiTech University, Shanghai, China;Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou, Zhejiang, China;

DOI  :  10.1038/s41421-022-00485-0

 received in 2022-01-05, accepted in 2022-10-19,  发布年份 2022

来源: Springer

【 摘 要 】

Unraveling cell fate plasticity during tissue homeostasis and repair can reveal actionable insights for stem cell biology and regenerative medicine. In the pancreas, it remains controversial whether lineage transdifferentiation among the exocrine cells occur under pathophysiological conditions. Here, to address this question, we used a dual recombinase-mediated genetic system that enables simultaneous tracing of pancreatic acinar and ductal cells using two distinct genetic reporters, avoiding the “ectopic” labeling by Cre-loxP recombination system. We found that acinar-to-ductal transdifferentiation occurs after pancreatic duct ligation or during caerulein-induced pancreatitis, but not during homeostasis or after partial pancreatectomy. On the other hand, pancreatic ductal cells contribute to new acinar cells after significant acinar cell loss. By genetic tracing of cell proliferation, we also quantify the cell proliferation dynamics and deduce the turnover rate of pancreatic exocrine lineages during homeostasis. Together, these results suggest that the lineage transdifferentiation happens between acinar cells and ductal cells in the pancreatic exocrine glands under specific conditions.

【 授权许可】

CC BY   
© The Author(s) 2023

【 图 表 】

41116_2022_35_Article_IEq441.gif

Fig. 1

41116_2022_35_Article_IEq419.gif

41116_2022_35_Article_IEq397.gif

Fig. 3

41116_2022_35_Article_IEq356.gif

41116_2022_35_Article_IEq335.gif

41116_2022_35_Article_IEq303.gif

41116_2022_35_Article_IEq287.gif