Single-Cell RNA-Seq Reveals the Heterogeneity of Cell Communications Between Schwann Cells and Fibroblasts Within the Microenvironment in Vestibular Schwannoma

Vestibular schwannomas (VS), which develop from the Schwann cells(SCs) of the vestibular nerve, are the most prevalent benign tumors of the cerebellopontine angle and internal auditory canal. Despite advances in treatment, the cellular components and mechanisms of VS tumor progression remain unclear. Here, we performed single-cell RNA-seq on clinically surgically isolated VS samples and sophisticated clarified their cellular composition, including the heterogeneous Schwann cell subtypes. Advanced bioinformatics analysis also revealed the associated biological functions, the differentiation trajectory and the transcriptional network of the SC subgroups. Furthermore, we also found that there was a tight intercellular communication between Schwann cells and tumor associated fibroblasts via integrin and growth factor signaling, and that the gene expression differences in SCs and fibroblasts determined the heterogeneity of cellular communication in different individuals. Our findings suggested a microenvironmental mechanism for the development of VS and also mapped the intratumoral heterogeneity landscape of VS.Funding Information: This work was supported by the Ministry of Science and Technology of the People’s Republic of China (2021ZD0201900), National Natural Science Foundation of China (No. 81870717 to DZ Yu, No. 81971240 to F Liu), Shanghai Municipal Education Commission–Gaofeng Clinical Medicine Grant (20191921) and Shanghai Municipal Commission of Science and Technology Declaration of Interests: There were no commercial or financial associations that may be considered as possible conflicts of interest during the study process. Ethics Approval Statement: The Shanghai Sixth People’s Hospital Institutional Ethics Review Board authorized all investigations involving human volunteers. Written informed consent was obtained from all participants.