Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways.
Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways.
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DOI：
10.1016/j.cell.2017.05.034
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发表时间：
2017-06-29
期刊：
影响因子：
64.5
通讯作者：
Julius D
中科院分区：
文献类型：
--
作者：
Bellono NW;Bayrer JR;Leitch DB;Castro J;Zhang C;O'Donnell TA;Brierley SM;Ingraham HA;Julius D
饮食、微生物和炎症因子调节肠-脑轴并影响从代谢到认知的生理过程。肠道上皮是检测此类病原体的主要部位，但人们对它如何与神经元件进行精确通讯知之甚少。血清素能肠嗜铬细胞（EC）被认为是通过充当化学传感器来实现这一作用的，但了解这些罕见而独特的细胞类型如何将化学传感信息传递给神经系统一直受到单细胞测量的缺乏和不可及性的阻碍。在这里，我们通过利用培养的肠类器官以及单细胞测量来阐明EC细胞的内在生物物理，药理学和遗传特性，从而规避了这一限制。我们表明，EC细胞表达特定的化学感受受体，是电兴奋的，并通过突触连接调节对多巴胺不敏感的初级传入神经纤维，使它们能够检测和识别环境，代谢和稳态信息从肠道直接到神经系统。使用类器官来表征肠道中罕见的化学感受细胞，阐明了它们的生物物理学，药理学和遗传学特性，并表明它们直接与神经感觉通路进行通信。
Dietary, microbial, and inflammatory factors modulate the gut-brain axis and influence physiological processes ranging from metabolism to cognition. The gut epithelium is a principle site for detecting such agents, but precisely how it communicates with neural elements is poorly understood. Serotonergic enterochromaffin (EC) cells are proposed to fulfill this role by acting as chemosensors, but understanding how these rare and unique cell types transduce chemosensory information to the nervous system has been hampered by their paucity and inaccessibility to single cell measurements. Here, we circumvent this limitation by exploiting cultured intestinal organoids together with single cell measurements to elucidate intrinsic biophysical, pharmacological, and genetic properties of EC cells. We show that EC cells express specific chemosensory receptors, are electrically excitable, and modulate serotoninsensitive primary afferent nerve fibers via synaptic connections, enabling them to detect and transduce environmental, metabolic, and homeostatic information from the gut directly to the nervous system. Use of organoids to characterize rare chemosensory cells in the gut elucidated their biophysical, pharmacological and genetic properties, and showed that they communicate directly with neural sensory pathways.
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