Department of Otolaryngology Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ear Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Neuro Oncol. 2024 Mar 4;26(3):444-457. doi: 10.1093/neuonc/noad201.
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 data set 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 vascular endothelial growth factor 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.
前庭神经鞘瘤（VS）是桥小脑角和内听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不同的生长模式。
使用单细胞 RNA 测序对 7 个 VS 样本和 2 个正常神经进行转录组分析。采用多重免疫荧光技术验证数据集结果。对 5 个正常神经和 44 个 VS 样本进行批量 RNA 测序，生成 VS 生长预测模型。
共注释了 83611 个细胞为 14 种不同的细胞类型。我们揭示了不同 VS 肿瘤的异质性。具有血管内皮生长因子标志物的 Schwann 细胞亚群通过 mRNA 分解代谢和肽合成与 VS 的快速生长显著相关。正常神经中的巨噬细胞主要为 M2 表型，而在生长缓慢和快速的 VS 之间，M1 和 M2 巨噬细胞的比例没有显著差异。VS 中正常纤维母细胞和血管细胞的空间分布被破坏。VS 中 Schwann 细胞和血管细胞之间的通讯增强。三个细胞簇与 VS 的快速生长显著相关，可细化批量 RNA 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。它可能有助于我们了解 VS 的不同临床表型，并有助于预测生长特征。分子亚型应纳入治疗考虑因素。
