Identification of cellular and noncellular components of mature intact human peripheral nerve

IF 3.9 3区 医学 Q1 CLINICAL NEUROLOGY Journal of the Peripheral Nervous System Pub Date : 2024-07-07 DOI:10.1111/jns.12643
Gabriela I. Aparicio, Jorge E. Quintero, Lauren Plum, Lingxiao Deng, Kristen Wanczyk, Miriam Henry, Evan Lynch, Michael Murphy, Greg A. Gerhardt, Craig G. van Horne, Paula V. Monje
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Abstract

Background and Aims

The goal of this study was to define basic constituents of the adult peripheral nervous system (PNS) using intact human nerve tissues.

Methods

We combined fluorescent and chromogenic immunostaining methods, myelin-selective fluorophores, and routine histological stains to identify common cellular and noncellular elements in aldehyde-fixed nerve tissue sections. We employed Schwann cell (SC)-specific markers, such as S100β, NGFR, Sox10, and myelin protein zero (MPZ), together with axonal, extracellular matrix (collagen IV, laminin, fibronectin), and fibroblast markers to assess the SC's relationship to myelin sheaths, axons, other cell types, and the acellular environment.

Results

Whereas S100β and Sox10 revealed mature SCs in the absence of other stains, discrimination between myelinating and non-myelinating (Remak) SCs required immunodetection of NGFR along with axonal and/or myelin markers. Surprisingly, our analysis of NGFR+ profiles uncovered the existence of at least 3 different novel populations of NGFR+/S100β− cells, herein referred to as nonglial cells, residing in the stroma and perivascular areas of all nerve compartments. An important proportion of the nerve's cellular content, including circa 30% of endoneurial cells, consisted of heterogenous S100β negative cells that were not associated with axons. Useful markers to identify the localization and diversity of nonglial cell types across different compartments were Thy1, CD34, SMA, and Glut1, a perineurial cell marker.

Interpretation

Our optimized methods revealed additional detailed information to update our understanding of the complexity and spatial orientation of PNS-resident cell types in humans.

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鉴定成熟完整人类周围神经的细胞和非细胞成分。
背景和目的本研究的目的是利用完整的人类神经组织确定成人周围神经系统(PNS)的基本成分:我们结合了荧光和色原免疫染色法、髓鞘选择性荧光团和常规组织学染色法,以确定醛固定神经组织切片中常见的细胞和非细胞元素。我们采用许旺细胞(SC)特异性标记物,如S100β、NGFR、Sox10和髓鞘蛋白零(MPZ),以及轴突、细胞外基质(胶原蛋白IV、层粘连蛋白、纤维连接蛋白)和成纤维细胞标记物来评估SC与髓鞘、轴突、其他细胞类型和无细胞环境的关系:结果:在没有其他染色剂的情况下,S100β和Sox10能显示成熟的SC,而区分髓鞘化和非髓化(Remak)SC则需要免疫检测NGFR以及轴突和/或髓鞘标记物。令人惊奇的是,我们对 NGFR+ 图谱的分析发现,至少存在 3 种不同的新型 NGFR+/S100β- 细胞群,在此称为非神经细胞,它们驻留在所有神经区的基质和血管周围区域。神经细胞的重要组成部分,包括约30%的内膜细胞,由与轴突无关的异源S100β阴性细胞组成。Thy1、CD34、SMA和Glut1(神经周围细胞标志物)是识别不同区段非神经胶质细胞类型定位和多样性的有用标志物:我们的优化方法揭示了更多详细信息,更新了我们对人类 PNS 驻留细胞类型的复杂性和空间定位的认识。
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来源期刊
CiteScore
6.10
自引率
7.90%
发文量
45
审稿时长
>12 weeks
期刊介绍: The Journal of the Peripheral Nervous System is the official journal of the Peripheral Nerve Society. Founded in 1996, it is the scientific journal of choice for clinicians, clinical scientists and basic neuroscientists interested in all aspects of biology and clinical research of peripheral nervous system disorders. The Journal of the Peripheral Nervous System is a peer-reviewed journal that publishes high quality articles on cell and molecular biology, genomics, neuropathic pain, clinical research, trials, and unique case reports on inherited and acquired peripheral neuropathies. Original articles are organized according to the topic in one of four specific areas: Mechanisms of Disease, Genetics, Clinical Research, and Clinical Trials. The journal also publishes regular review papers on hot topics and Special Issues on basic, clinical, or assembled research in the field of peripheral nervous system disorders. Authors interested in contributing a review-type article or a Special Issue should contact the Editorial Office to discuss the scope of the proposed article with the Editor-in-Chief.
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