Journal Article

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

Shew, Matthew, Puram, Sidharth V., Barrett, Thomas F., Yim, Aldrin K. Y., Zipfel, Gregory J., Sweeney, Alex D., Mahlokozera, Tatenda, Pugazenthi, Sangami, Khan, Saad M., Durakovic, Nedim, Buchman, Craig A., Wick, Cameron C., Mullins, Riley D. Z., Patel, Bhuvic, Chicoine, Michael R., Herzog, Jacques A., Petti, Allegra A., Patel, Akash J., Osbun, Joshua W., Kim, Albert H.

2024

Overview

Vestibular schwannomas (VS) are benign tumors that lead to significant neurologic and otologic morbidity. How VS heterogeneity and the tumor microenvironment (TME) contribute to VS pathogenesis remains poorly understood. In this study, we perform scRNA-seq on 15 VS, with paired scATAC-seq ( n  = 6) and exome sequencing ( n  = 12). We identify diverse Schwann cell (SC), stromal, and immune populations in the VS TME and find that repair-like and MHC-II antigen-presenting SCs are associated with myeloid cell infiltrate, implicating a nerve injury-like process. Deconvolution analysis of RNA-expression data from 175 tumors reveals Injury-like tumors are associated with larger tumor size, and scATAC-seq identifies transcription factors associated with nerve repair SCs from Injury-like tumors. Ligand-receptor analysis and in vitro experiments suggest that Injury-like VS-SCs recruit myeloid cells via CSF1 signaling. Our study indicates that Injury-like SCs may cause tumor growth via myeloid cell recruitment and identifies molecular pathways that may be therapeutically targeted. Vestibular schwannomas are benign tumours which can lead to neurological symptoms and morbidity. Here, the authors use single cell RNA-seq and ATAC-seq to identify Schwann cell subtypes in the tumour microenvironment which mimic a nerve injury phenotype.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/106 / 13/51 / 38/23 / 38/39 / 45/91 / 631/67/1922 / 631/67/2329 / Ecosystem / Gene expression / Heterogeneity / Humanities and Social Sciences / Humans / Injuries / Injury analysis / Major histocompatibility complex / Morbidity / multidisciplinary / Multiomics / Myeloid cells / Nerves / Neuroma, Acoustic - genetics / Neuroma, Acoustic - metabolism / Neuroma, Acoustic - pathology / Pathogenesis / Phenotypes / Schwann cells / Schwann Cells - metabolism / Science / Science (multidisciplinary) / Signal Transduction - physiology / Single-Cell Analysis / Transcription factors / Tumor Microenvironment / Tumors / Vestibular system