Scopus list of publications for January 21, 2024
Single-cell multi-omic analysis of the vestibular schwannoma ecosystem uncovers a nerve injury-like state
(2024) Nature Communications, 15 (1), art. no. 478, .
Barrett, T.F.a , Patel, B.b , Khan, S.M.c d , Mullins, R.D.Z.a e , Yim, A.K.Y.e , Pugazenthi, S.b , Mahlokozera, T.b , Zipfel, G.J.b f , Herzog, J.A.a f , Chicoine, M.R.g , Wick, C.C.a f , Durakovic, N.a f , Osbun, J.W.b , Shew, M.a f , Sweeney, A.D.h , Patel, A.J.h i j , Buchman, C.A.a f , Petti, A.A.c d , Puram, S.V.a e k , Kim, A.H.b e f
a Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, United States
b Department of Neurological Surgery, Washington University School of Medicine, St. Louis, MO, United States
c Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, United States
d Brain Tumor Immunology and Immunotherapy Program, Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States
e Department of Genetics, Washington University School of Medicine, St. Louis, MO, United States
f Brain Tumor Center, Washington University School of Medicine/Siteman Cancer Center, St. Louis, MO, United States
g Department of Neurological Surgery, University of Missouri School of Medicine, Columbia, MO, United States
h Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, United States
i Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
j Jan and Dan Duncan Neurological Research Institute, Texas Children’s Hospital, Houston, TX, United States
k Siteman Cancer Center, Washington University in St. Louis, St. Louis, MO, United States
Abstract
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. © 2023, The Author(s).
Funding details
National Institutes of HealthNIH5R25NS090978-08
National Institute on Deafness and Other Communication DisordersNIDCDT32DC000022
Doris Duke Charitable FoundationDDCF
Foundation for Barnes-Jewish HospitalFBJH
Document Type: Article
Publication Stage: Final
Source: Scopus