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. 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)是肠神经系统中的主要细胞类型，但其身份特征与在胃肠功能中的作用尚未得到明确界定与分类。本研究借助优化后的单细胞核RNA测序（single nucleus RNA-sequencing）方法，鉴定出不同的肠胶质细胞分子亚型，并明确了其形态学特征与空间分布多样性。本研究发现一类功能特化的肠胶质细胞生物传感器亚型，并将其命名为“枢纽细胞（hub cells）”。从成年肠胶质枢纽细胞中敲除机械敏感离子通道PIEZO2（而非其他肠胶质细胞亚型），可导致小鼠出现肠道运动障碍与胃排空功能异常。上述研究结果揭示了不同肠胶质细胞亚型在肠道健康中的多维度功能，并提示靶向肠胶质细胞的疗法可推动胃肠道疾病的治疗进展。 本研究通过CitraPrep试剂分离C57Bl/6小鼠完整成年十二指肠的细胞核，并采用snRNAseq进行测序分析。