Hall Shaina, Liu Shixuan, Liang Irene, Schulz Shawn, Ezran Camille, Tan Mingqian, Kuo Christin S
Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America.
Department of Biochemistry, Stanford University School of Medicine, Stanford, California, United States of America.
PLoS One. 2024 Dec 2;19(12):e0310303. doi: 10.1371/journal.pone.0310303. eCollection 2024.
Peripheral glia are important regulators of diverse physiologic functions yet their molecular distinctions and locations in almost all visceral organs are not well-understood. We performed a systematic analysis of peripheral glia, focusing on the lung and leveraging single cell RNA sequencing (scRNA-seq) analysis to characterize their cellular and molecular features. Using in vivo lineage studies, we characterized the anatomic, cellular, and molecular features of the Sox10+ glial lineage of the mouse lung. Using high-resolution imaging, we quantified the distribution and cellular morphologies of myelinating, non-myelinating, satellite, and terminal glial cells with their intricate extensions along peripheral nerves, including terminals at specialized neurosensory structures within the lung. Spatial analysis of selectively expressed myelinating (periaxin/Prx, claudin 19/Cldn) or non-myelinating (sodium channel/Scn7a) glial cell genes identified by scRNA-seq analysis revealed molecularly distinct populations surrounding myelinated nerve fibers in the lung. To extend this analysis to primates and other organs, we extracted rare peripheral glial cells in whole organism scRNA-seq atlases of mouse lemur and human. Our cross-species data analysis and integration of scRNA-seq data of ~700 peripheral glial cells from mouse, mouse lemur, and human glial cells identified conserved gene expression of molecularly distinct peripheral glial cell populations. This foundational knowledge facilitates subsequent functional studies targeting molecularly distinct subsets of peripheral glia and integrating them into organ-specific disorders of autonomic dysregulation. In addition, our cross-species analysis identifying conserved gene expression patterns and glial networks in extrapulmonary organs provides a valuable resource for studying the functional role of peripheral glia in multiorgan human diseases.
外周神经胶质细胞是多种生理功能的重要调节因子，然而，它们在几乎所有内脏器官中的分子差异和位置尚未得到充分了解。我们对外周神经胶质细胞进行了系统分析，重点关注肺，并利用单细胞RNA测序（scRNA-seq）分析来表征其细胞和分子特征。通过体内谱系研究，我们表征了小鼠肺中Sox10+神经胶质谱系的解剖、细胞和分子特征。利用高分辨率成像，我们量化了有髓、无髓、卫星和终末神经胶质细胞的分布和细胞形态，以及它们沿外周神经的复杂延伸，包括肺内特殊神经感觉结构处的终末。对通过scRNA-seq分析鉴定出的选择性表达的有髓（外周髓鞘蛋白/Prx、紧密连接蛋白19/Cldn）或无髓（钠通道/Scn7a）神经胶质细胞基因进行空间分析，揭示了肺中有髓神经纤维周围分子上不同的细胞群。为了将这种分析扩展到灵长类动物和其他器官，我们从小鼠狐猴和人类的全生物体scRNA-seq图谱中提取了罕见的外周神经胶质细胞。我们对来自小鼠、小鼠狐猴和人类神经胶质细胞的约700个外周神经胶质细胞的跨物种数据分析和scRNA-seq数据整合，确定了分子上不同的外周神经胶质细胞群的保守基因表达。这一基础知识有助于后续针对外周神经胶质细胞分子上不同亚群的功能研究，并将它们整合到自主神经调节异常的器官特异性疾病中。此外，我们的跨物种分析确定了肺外器官中保守的基因表达模式和神经胶质网络，为研究外周神经胶质细胞在多器官人类疾病中的功能作用提供了宝贵资源。
