单细胞转录组揭示前庭神经鞘瘤的异质性和微环境。
Single-cell transcriptomes reveal the heterogeneity and microenvironment of vestibular schwannoma.
发表日期:2023 Oct 20
作者:
Zirong Huo, Zhaohui Wang, Huahong Luo, Dilihumaer Maimaitiming, Tao Yang, Huihui Liu, Huipeng Li, Hao Wu, Zhihua Zhang
来源:
NEURO-ONCOLOGY
摘要:
前庭神经鞘瘤(VS)是桥小脑角和内耳道最常见的良性肿瘤。阐明 VS 的异质细胞成分可以深入了解其各种生长模式。使用单细胞 RNA 测序来分析 7 个 VS 样本和 2 个正常神经的转录组。采用多重免疫荧光来验证数据集结果。对 5 个正常神经和 44 个 VS 样本进行批量 RNA 测序,以生成 VS 生长的预测模型。总共 83,611 个细胞被注释为 14 种不同的细胞类型。我们发现了不同 VS 肿瘤的异质性。具有 VEGFA 生物标志物的雪旺细胞亚群通过 mRNA 分解代谢和肽生物合成与 VS 快速生长显着相关。正常神经中的巨噬细胞大部分为M2表型,而缓慢生长和快速生长的VS之间M1和M2巨噬细胞的比例没有显着差异。 VS 中成纤维细胞和血管细胞的正常空间分布被破坏。与正常神经相比,VS 中雪旺细胞和血管细胞之间的通讯增强。三个细胞簇与 VS 的快速生长显着相关,并且可以细化体 RNA 中的生长分类。我们的研究结果为单细胞水平的 VS 微环境提供了新的见解。它可以增强我们对 VS 不同临床表型的理解,并有助于预测生长特征。分子亚型应纳入治疗考虑因素中。© 作者 2023。由牛津大学出版社代表神经肿瘤学会出版。版权所有。如需权限,请发送电子邮件至:journals.permissions@oup.com。
Vestibular schwannoma (VS) is the most common benign tumor in the cerebellopontine angle and internal auditory canal. Illustrating the heterogeneous cellular components of VS could provide insights into its various growth patterns.Single-cell RNA sequencing was used to profile transcriptomes from 7 VS samples and 2 normal nerves. Multiplex immunofluorescence was employed to verify the dataset results. Bulk RNA sequencing was conducted on 5 normal nerves and 44 VS samples to generate a prediction model for VS growth.A total of 83,611 cells were annotated as 14 distinct cell types. We uncovered the heterogeneity in distinct VS tumors. A subset of Schwann cells with the VEGFA biomarker was significantly associated with fast VS growth through mRNA catabolism and peptide biosynthesis. The macrophages in the normal nerves were largely of the M2 phenotype, while no significant differences in the proportions of M1 and M2 macrophages were found between slow-growing and fast-growing VS. The normal spatial distribution of fibroblasts and vascular cells was destroyed in VS. The communications between Schwann cells and vascular cells were strengthened in VS compared with those in the normal nerve. Three cell clusters were significantly associated with fast VS growth and could refine the growth classification in bulk RNA.Our findings offer novel insights into the VS microenvironment at the single-cell level. It may enhance our understanding of the different clinical phenotypes of VS and help predict growth characteristics. Molecular subtypes should be included in the treatment considerations.© The Author(s) 2023. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.