Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, USA.
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
Genome Med. 2022 May 10;14(1):49. doi: 10.1186/s13073-022-01051-9.
Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples.
Single-cell RNA sequencing of seven non-tumor-associated human dura samples and six primary meningioma tumor samples (4 matched and 2 non-matched) was performed. Cell type identities, gene expression profiles, and T cell receptor expression were analyzed. Copy number variant (CNV) analysis was performed to identify putative tumor cells and analyze intratumoral CNV heterogeneity. Immunohistochemistry and imaging mass cytometry was performed on selected samples to validate protein expression and reveal spatial localization of select protein markers.
In this study, we use single-cell RNA sequencing to perform the first characterization of both non-tumor-associated human dura and primary meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, we characterize a functionally diverse and heterogenous landscape of non-immune cells including endothelial cells and fibroblasts. Through imaging mass cytometry, we highlight the spatial relationship among immune cell types and vasculature in non-tumor-associated dura. Utilizing T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. Finally, we report copy number variant heterogeneity within our meningioma samples.
Our comprehensive investigation of both the immune and non-immune cellular landscapes of human dura and meningioma at single-cell resolution builds upon previously published data in murine models and provides new insight into previously uncharacterized roles of human dura.
最近对脑膜的研究强调了硬脑膜层在中枢神经系统免疫监视中的重要性，超出了纯粹的结构作用。然而，我们对脑膜的理解主要来自于临床前模型的应用，而不是人类样本。
对 7 个非肿瘤相关的人类硬脑膜样本和 6 个原发性脑膜瘤肿瘤样本（4 个匹配和 2 个非匹配）进行单细胞 RNA 测序。分析细胞类型身份、基因表达谱和 T 细胞受体表达。进行拷贝数变异（CNV）分析，以识别潜在的肿瘤细胞并分析肿瘤内 CNV 异质性。对选定的样本进行免疫组织化学和成像质谱细胞术检测，以验证蛋白质表达并揭示选择蛋白标记物的空间定位。
在这项研究中，我们使用单细胞 RNA 测序首次对非肿瘤相关的人类硬脑膜和原发性脑膜瘤样本进行了特征描述。首先，我们揭示了人类硬脑膜中复杂的免疫微环境，其转录组与脑膜瘤明显不同。此外，我们还描述了一种功能多样且异质的非免疫细胞景观，包括内皮细胞和成纤维细胞。通过成像质谱细胞术，我们突出了非肿瘤相关硬脑膜中免疫细胞类型与脉管系统之间的空间关系。利用 T 细胞受体测序，我们显示了匹配的硬脑膜和脑膜瘤样本之间存在显著的 TCR 重叠。最后，我们报告了我们脑膜瘤样本中的拷贝数变异异质性。
我们对人类硬脑膜和脑膜瘤的免疫和非免疫细胞景观进行了单细胞分辨率的全面研究，这是对以前在鼠模型中发表的数据的扩展，并为以前未被描述的人类硬脑膜的作用提供了新的见解。
