Enteric glial hub cells coordinate intestinal motility

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. Overall design: Nuclei from the whole adult duodenum of C57Bl/6 mice were isolated using CitraPrep and analyzed using snRNAseq

肠胶质细胞（Enteric glia）是肠神经系统中占主导地位的细胞类型，但其在胃肠功能中的身份与作用尚未得到充分界定。本研究利用优化后的单细胞核RNA测序（single nucleus RNA-sequencing）方法，鉴定出了不同的肠胶质细胞分子亚型，并明确了其形态学与空间分布的多样性。本研究发现了一类功能特化的肠胶质细胞生物传感器亚型，我们将其命名为"枢纽细胞（hub cells）"。在成年小鼠的肠胶质枢纽细胞中敲除机械感受离子通道PIEZO2（而非其他肠胶质细胞亚型），会导致小鼠出现肠道动力障碍与胃排空缺陷。这些研究结果揭示了不同肠胶质细胞亚型在肠道健康中的多方面功能，并提示靶向肠胶质细胞的疗法有望推动胃肠疾病的治疗进展。实验设计概述：利用CitraPrep技术分离C57Bl/6成年小鼠全十二指肠中的细胞核，并通过单细胞核RNA测序（snRNAseq）进行分析。