Single-cell sequencing reveals the cell map and transcriptional network of sporadic vestibular schwannoma

Abstract

In this study, based on three tumor samples obtained from patients with sporadic vestibular schwannoma, 32,011 cells were obtained by single-cell transcriptome sequencing, and 22,309 high-quality cells were obtained after quality control and double cells removal. Then, 18 cell clusters were obtained after cluster analysis, and each cluster was annotated as six types of cells. Afterward, an in-depth analysis was conducted based on the defined six cell clusters, including characterizing the functional characteristics of each cell subtype, describing the cell development and differentiation pathway, exploring the interaction between cells, and analyzing the transcriptional regulatory network within the clusters. Based on these four dimensions, various types of cells in sporadic vestibular schwannoma tumor tissues were described in detail. For the first time, we expanded on the functional state of cell clusters that have been reported and described Schwann cells in the peripheral nervous system, which have not been reported in previous studies. Combined with the data of sporadic vestibular schwannoma and normal tissues in the gene expression omnibus (GEO) database, the candidate biomarkers of sporadic vestibular schwannoma were explored. Overall, this study described the single-cell map of sporadic vestibular schwannoma for the first time, revealing the functional state and development trajectory of different cell types. Combined with the analysis of data in the GEO database and immunohistochemical verification, it was concluded that HLA-DPB1 and VSIG4 may be candidate biomarkers and potential therapeutic targets for patients with sporadic vestibular schwannoma.

Single-cell RNA sequencing analysis of vestibular schwannoma reveals functionally distinct macrophage subsets

“…There is limited information available in literature on the cellular profile of VS using single-cell analysis. Previous work has focused on single-cell analysis of Schwann cells and the interactions between Schwann cells and fibroblasts [ 46 , 47 ]. Our scRNAseq data further confirms the presence of several cellular subsets in VS including Schwann cells, fibroblasts and immune cells, such as macrophages and T cells.…”

Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state

“…Our single-cell multi-omic analysis of sporadic VS represents an important step in understanding the intraand inter-tumoral heterogeneity underlying their pathogenesis and progression. Recent studies have also profiled sporadic VS with scRNAseq 56,57 . Similar to these recent reports, we found an unexpected diversity within the SC compartment of these tumors, with loss of the myelinating phenotype and varying degrees of myeloid cell infiltrate being consistent findings across studies.…”

Single-cell sequencing: a powerful technique to understand the pathophysiology of auditory disorders

“…By applying SCS to VS tissue samples, the different cell types and factors in these tumors as well as candidate biomarkers of VS can be identified leading to the discovery of potential drug targets. A study performed SCS on three human tissue samples of sporadic VS and was able to identify six cell types involved in the tumor microenvironment: Schwann cells, myeloid cells, fibroblasts, lymphocytes (B and T cells), and endothelial cells (Yidian et al, 2022). Six Schwann cell subgroups were identified based on antigen presenting genes and HLA phenotypes.…”

“…Cellular subgroup SC-C4 was correlated to chemokine activation and SC-C5 to myelination, suggesting the high heterogeneity of the expression profiles and function of this cell type in VS. Analysis of transcription factors revealed SC-C5 expressed TEAD4, involved in the Hippo signaling pathway which induces apoptosis and limits proliferation (Yidian et al, 2022). Analysis of the myeloid cell population, and more particularly a subtype of monocytes, activated PI3K a transduction pathway involved in chemotherapy resistance.…”

“…Through SCS, cellular interactions were also studied, and allowed to identify specific cellular links, especially those between fibroblasts and immune cells. Two different fibroblast clusters were found to be mainly involved in the CXCL signaling pathway, promoting angiogenesis in tumor tissue (Yidian et al, 2022). The application of SCS in sporadic VS revealed fundamental characteristics on cellular heterogeneity, microenvironment, and molecular pathways, paving the way for specific drug development.…”