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肠道神经胶质中枢细胞协调肠道蠕动。

Enteric glial hub cells coordinate intestinal motility.

作者信息

Scavuzzo Marissa A, Letai Katherine C, Maeno-Hikichi Yuka, Wulftange William J, Shah Isha K, Rameshbabu Jeyashri S, Tomar Alka, Shick H Elizabeth, Shah Aakash K, Xiong Ying, Cohn Erin F, Allan Kevin C, Tesar Paul J

机构信息

Department of Genetics and Genome Sciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA.

出版信息

bioRxiv. 2023 Jun 9:2023.06.07.544052. doi: 10.1101/2023.06.07.544052.

DOI:10.1101/2023.06.07.544052
PMID:37333182
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10274798/
Abstract

Enteric glia are the predominant cell type in the enteric nervous system yet their identities and roles in gastrointestinal function are not well classified. Using our optimized single nucleus RNA-sequencing method, we identified distinct molecular classes of enteric glia and defined their morphological and spatial diversity. Our findings revealed a functionally specialized biosensor subtype of enteric glia that we call "hub cells." Deletion of the mechanosensory ion channel PIEZO2 from adult enteric glial hub cells, but not other subtypes of enteric glia, led to defects in intestinal motility and gastric emptying in mice. These results provide insight into the multifaceted functions of different enteric glial cell subtypes in gut health and emphasize that therapies targeting enteric glia could advance the treatment of gastrointestinal diseases.

摘要

肠神经胶质细胞是肠神经系统中的主要细胞类型,然而它们在胃肠道功能中的身份和作用尚未得到很好的分类。利用我们优化的单核RNA测序方法,我们鉴定出了肠神经胶质细胞的不同分子类别,并定义了它们的形态和空间多样性。我们的研究结果揭示了一种功能特化的肠神经胶质细胞生物传感器亚型,我们将其称为“枢纽细胞”。从小鼠成年肠神经胶质枢纽细胞而非其他肠神经胶质细胞亚型中删除机械感觉离子通道PIEZO2,会导致肠道蠕动和胃排空出现缺陷。这些结果为不同肠神经胶质细胞亚型在肠道健康中的多方面功能提供了见解,并强调针对肠神经胶质细胞的疗法可能会推动胃肠道疾病的治疗。

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Enteric glial hub cells coordinate intestinal motility.肠道神经胶质中枢细胞协调肠道蠕动。
bioRxiv. 2023 Jun 9:2023.06.07.544052. doi: 10.1101/2023.06.07.544052.
2
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J Neurosci. 2022 Nov 16;42(46):8694-8708. doi: 10.1523/JNEUROSCI.2379-20.2022. Epub 2022 Nov 1.
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本文引用的文献

1
PIEZO2 in somatosensory neurons controls gastrointestinal transit.机械敏感离子通道蛋白 2 于躯体感觉神经元中控制胃肠道传输。
Cell. 2023 Aug 3;186(16):3386-3399.e15. doi: 10.1016/j.cell.2023.07.006.
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A cellular taxonomy of the adult human spinal cord.成人脊髓的细胞分类。
Neuron. 2023 Feb 1;111(3):328-344.e7. doi: 10.1016/j.neuron.2023.01.007.
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APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes.载脂蛋白 E4 通过调控少突胶质细胞胆固醇影响髓鞘形成。
Nature. 2022 Nov;611(7937):769-779. doi: 10.1038/s41586-022-05439-w. Epub 2022 Nov 16.
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Functional Intraregional and Interregional Heterogeneity between Myenteric Glial Cells of the Colon and Duodenum in Mice.功能性区域性和区域性之间的异质性在小鼠的结肠和十二指肠肌间神经胶质细胞中。
J Neurosci. 2022 Nov 16;42(46):8694-8708. doi: 10.1523/JNEUROSCI.2379-20.2022. Epub 2022 Nov 1.
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Single-cell analyses of axolotl telencephalon organization, neurogenesis, and regeneration.蝾螈端脑组织、神经发生和再生的单细胞分析。
Science. 2022 Sep 2;377(6610):eabp9262. doi: 10.1126/science.abp9262.
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Pyramidal neuron subtype diversity governs microglia states in the neocortex.锥体神经元亚型多样性控制大脑新皮层中的小胶质细胞状态。
Nature. 2022 Aug;608(7924):750-756. doi: 10.1038/s41586-022-05056-7. Epub 2022 Aug 10.
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Mapping genomic loci implicates genes and synaptic biology in schizophrenia.基因组定位研究提示精神分裂症的发病与基因及突触生物学有关。
Nature. 2022 Apr;604(7906):502-508. doi: 10.1038/s41586-022-04434-5. Epub 2022 Apr 8.
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Rare coding variants in ten genes confer substantial risk for schizophrenia.十个基因中的罕见编码变异赋予精神分裂症的显著风险。
Nature. 2022 Apr;604(7906):509-516. doi: 10.1038/s41586-022-04556-w. Epub 2022 Apr 8.
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Computation and visualization of cell-cell signaling topologies in single-cell systems data using Connectome.使用 Connectome 计算和可视化单细胞系统数据中的细胞间信号拓扑结构。
Sci Rep. 2022 Mar 9;12(1):4187. doi: 10.1038/s41598-022-07959-x.
10
Autism genes converge on asynchronous development of shared neuron classes.自闭症基因集中于共享神经元类别的异步发育。
Nature. 2022 Feb;602(7896):268-273. doi: 10.1038/s41586-021-04358-6. Epub 2022 Feb 2.