Neuroendocrinology of the lung revealed by single-cell RNA sequencing.
Neuroendocrinology of the lung revealed by single-cell RNA sequencing.
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DOI：
10.7554/elife.78216
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发表时间：
2022-12-05
期刊：
影响因子：
7.7
通讯作者：
Krasnow MA
中科院分区：
文献类型：
--
作者：
Kuo CS;Darmanis S;Diaz de Arce A;Liu Y;Almanzar N;Wu TT;Quake SR;Krasnow MA
肺神经内分泌细胞（PNEC）是通过感觉神经元和局部通过降钙素基因相关肽（CGRP）和γ-氨基丁酸（GABA）将气道状态传递到大脑的感觉上皮细胞。在各种物种中已经检测到其他几种神经肽和神经递质，但PNEC信号的数量，靶点，功能和保守性在很大程度上是未知的。我们使用scRNAseq分析了数百种罕见的小鼠和人类PNEC。这揭示了超过40个PNEC神经肽和肽激素基因，大多数细胞表达5-18个基因的独特组合。肽被包装在单独的囊泡中，它们的释放可能受到不同的，多模式的传感器组合的调节，我们显示每个PNEC表达。肽受体的表达预测了一系列的局部细胞靶点，我们表明新的PNEC信号血管紧张素直接激活一种亚型的支配感觉神经元。许多信号缺乏肺靶点，因此可能具有内分泌活性，如PNEC衍生的类癌肿瘤。PNEC是一个非常丰富和多样的信号中枢，可与肠内分泌系统相媲美。
Pulmonary neuroendocrine cells (PNECs) are sensory epithelial cells that transmit airway status to the brain via sensory neurons and locally via calcitonin gene-related peptide (CGRP) and γ- aminobutyric acid (GABA). Several other neuropeptides and neurotransmitters have been detected in various species, but the number, targets, functions, and conservation of PNEC signals are largely unknown. We used scRNAseq to profile hundreds of the rare mouse and human PNECs. This revealed over 40 PNEC neuropeptide and peptide hormone genes, most cells expressing unique combinations of 5–18 genes. Peptides are packaged in separate vesicles, their release presumably regulated by the distinct, multimodal combinations of sensors we show are expressed by each PNEC. Expression of the peptide receptors predicts an array of local cell targets, and we show the new PNEC signal angiotensin directly activates one subtype of innervating sensory neuron. Many signals lack lung targets so may have endocrine activity like those of PNEC-derived carcinoid tumors. PNECs are an extraordinarily rich and diverse signaling hub rivaling the enteroendocrine system.