2. Academic Validation
  3. Use of a dual genetic system to decipher exocrine cell fate conversions in the adult pancreas

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

  • Cell Discov. 2023 Jan 3;9(1):1. doi: 10.1038/s41421-022-00485-0.
Huan Zhao # 1,  Xiuzhen Huang # 1,  Zixin Liu # 1,  Liang Lai 2,  Ruilin Sun 2,  Ruling Shen 3,  Yan Li 1,  Lingjuan He 4,  Wenjuan Pu 1,  Zan Lv 1,  Yi Li 1,  Ximeng Han 1,  Xiuxiu Liu 1,  Bin Zhou 5 6 7
Affiliations

Affiliations

  • 1 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.
  • 2 Shanghai Model Organisms Center, Inc., Shanghai, China.
  • 3 Shanghai Laboratory Animal Research Center, Shanghai, China.
  • 4 School of Life Sciences, Westlake University, Hangzhou, Zhejiang, China.
  • 5 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. zhoubin@sibs.ac.cn.
  • 6 School of Life Science and Technology, ShanghaiTech University, Shanghai, China. zhoubin@sibs.ac.cn.
  • 7 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. zhoubin@sibs.ac.cn.
  • # Contributed equally.
PMID: 36596774 DOI: 10.1038/s41421-022-00485-0
Abstract

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.

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