【摘 要】
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The gastric epithelium continuously self-renews throughout life, driven by limited reservoirs of resident Lgr5+ adult stem cells.Here, we employ an Lgr5-DTR
【机 构】
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A*STARInstituteofMedicalBiology,138648SingaporeCentreforRegenerativeMedicine,TheUniversityofEdinburg
论文部分内容阅读
The gastric epithelium continuously self-renews throughout life, driven by limited reservoirs of resident Lgr5+ adult stem cells.Here, we employ an Lgr5-DTR mouse model to ablate Lgr5+ gastric cells in vivo as a means of evaluating their contribution to epithelial homeostasis and disease in the glandular stomach.Long-term ablation of the Lgr5+ cell compartment severely impairs epithelial homeostasis in both the pyloric antrum and the corpus, but regeneration occurs following cessation of DT treatment, implicating the existence of stem cell plasticity.We additionally characterize the transcriptome of the pyloric Lgr5+ stem cells, revealing new gastric stem cell-specific markers that can be used to selectively target cancer-causing mutations to the Lgr5+ stem cell compartment in the stomach as a means of evaluating their contribution to gastric cancer initiation.Finally, we present a novel gastric epithelial-specific Cre line that will be an invaluable tool for generating mouse models of human gastric cancer,together with an Lgr5-2A-CreERT2 model that reveals potential stem cell populations in organs such as the liver and kidney.
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