New trends and perspectives in the function of non-neuronal acetylcholine in crypt-villus organoids in mice
New trends and perspectives in the function of non-neuronal acetylcholine in crypt-villus organoids in mice
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小鼠隐窝绒毛类器官中非神经元乙酰胆碱功能的新趋势和新观点
DOI：
10.1007/7651_2016_1
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Takahashi T.
中科院分区：
文献类型：
--
作者：
Takahashi T. and Shiraishi A.;Takahashi T.;Takahashi T.
乙酰胆碱（Acetylcholine，ACh）是一种存在于哺乳动物中枢、副交感神经和神经肌肉突触中的神经递质。然而，非神经元ACh也被预测作为局部细胞信号分子。非神经元乙酰胆碱在肠道中的存在的生理意义仍然不清楚。在这里，使用缺乏神经和免疫细胞的培养的隐窝-绒毛类器官的实验使我们表明，内源性ACh在肠上皮中合成，通过激活毒蕈碱ACh受体（mAChR）来引起类器官的生长和分化。培养类器官的提取物表现出明显的乙酰胆碱合成能力，这是敏感的胆碱乙酰转移酶的有效抑制剂。用卡巴胆碱处理类器官下调类器官的生长和每种上皮细胞类型的标记基因的表达。另一方面，mAChR拮抗剂增强Lgr 5阳性干细胞的生长和分化。总的来说，我们的数据提供的证据表明，内源性乙酰胆碱释放小鼠肠上皮细胞通过mAChRs维持肠上皮细胞的生长和分化的稳态。
Acetylcholine (ACh) is a neurotransmitter that is present in central, parasympathetic, and neuromuscular synapses of mammals. However, non-neuronal ACh is also predicted to function as a local cell signaling molecule. The physiological significance of the presence of non-neuronal ACh in the intestine remains unclear. Here, experiments using cultured crypt–villus organoids that lack nerve and immune cells led us to suggest that endogenous ACh is synthesized in the intestinal epithelium to evoke growth and differentiation of the organoids through activation of muscarinic ACh receptors (mAChRs). Extracts of cultured organoids exhibited a noticeable capacity for ACh synthesis that was sensitive to a potent inhibitor of choline acetyltransferase. Treatment of organoids with carbachol downregulated growth of organoids and expression of marker genes for each epithelial cell type. On the other hand, mAChR antagonists enhanced growth and differentiation of Lgr5-positive stem cells. Collectively, our data provide evidence that endogenous ACh released from mouse intestinal epithelium maintains the homeostasis of intestinal epithelial cell growth and differentiation via mAChRs.