@article{252cc8708a4b4f2fb758426ab3c2b130,
title = "Single-cell profiling of human dura and meningioma reveals cellular meningeal landscape and insights into meningioma immune response",
abstract = "Background: Recent investigations of the meninges have highlighted the importance of the dura layer in central nervous system immune surveillance beyond a purely structural role. However, our understanding of the meninges largely stems from the use of pre-clinical models rather than human samples. Methods: Single-cell RNA sequencing of seven non-tumor-associated human dura samples and six primary meningioma tumor samples (4 matched and 2 non-matched) was performed. Cell type identities, gene expression profiles, and T cell receptor expression were analyzed. Copy number variant (CNV) analysis was performed to identify putative tumor cells and analyze intratumoral CNV heterogeneity. Immunohistochemistry and imaging mass cytometry was performed on selected samples to validate protein expression and reveal spatial localization of select protein markers. Results: In this study, we use single-cell RNA sequencing to perform the first characterization of both non-tumor-associated human dura and primary meningioma samples. First, we reveal a complex immune microenvironment in human dura that is transcriptionally distinct from that of meningioma. In addition, we characterize a functionally diverse and heterogenous landscape of non-immune cells including endothelial cells and fibroblasts. Through imaging mass cytometry, we highlight the spatial relationship among immune cell types and vasculature in non-tumor-associated dura. Utilizing T cell receptor sequencing, we show significant TCR overlap between matched dura and meningioma samples. Finally, we report copy number variant heterogeneity within our meningioma samples. Conclusions: Our comprehensive investigation of both the immune and non-immune cellular landscapes of human dura and meningioma at single-cell resolution builds upon previously published data in murine models and provides new insight into previously uncharacterized roles of human dura.",
keywords = "Dura, Imaging mass cytometry, Meninges, Single-cell RNA sequencing",
author = "Wang, {Anthony Z.} and Bowman-Kirigin, {Jay A.} and Rupen Desai and Kang, {Liang I.} and Patel, {Pujan R.} and Bhuvic Patel and Khan, {Saad M.} and Diane Bender and Marlin, {M. Caleb} and Jingxian Liu and Osbun, {Joshua W.} and Leuthardt, {Eric C.} and Chicoine, {Michael R.} and Dacey, {Ralph G.} and Zipfel, {Gregory J.} and Kim, {Albert H.} and DeNardo, {David G.} and Petti, {Allegra A.} and Dunn, {Gavin P.}",
note = "Funding Information: AZW was supported by the Medical Scientist Training Program at Washington University in St. Louis, and JABK was supported in part by the Medical Scientist Training Program at Washington University in St. Louis and in part by a F30 grant. Funding Information: We thank the Genome Technology Access Center at the McDonnell Genome Institute at Washington University School of Medicine for help with genomics services. We thank the Center for Reproductive Health Sciences at Washington University School of Medicine for help with tissue embedding and sectioning. We would also like to thank the Arthritis & Clinical Immunology Human Phenotyping Core at the Oklahoma Medical Research Foundation for assistance with Hyperion Imaging Mass Cytometry data acquisition. Funding Information: Immunohistochemical slides of dura were imaged on a Zeiss LSM 880 Airyscan Confocal Microscope which was purchased with support from the Office of Research Infrastructure Programs (ORIP), a part of the NIH Office of the Director under grant OD021629, and imaging was performed in part through the use of Washington University Center for Cellular Imaging (WUCCI) supported by Washington University School of Medicine, The Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (CDI-CORE-2015-505 and CDI-CORE-2019-813) and the Foundation for Barnes-Jewish Hospital (3770 and 4642). This work was also supported, in part, by the Bursky Center for Human Immunology and Immunotherapy Programs at Washington University, Immunomonitoring Laboratory. Funding Information: The Genome Technology Access Center at the McDonnell Genome Institute at Washington University School of Medicine is partially supported by NCI Cancer Center Support Grant #P30 CA91842 to the Siteman Cancer Center and by ICTS/CTSA Grant# UL1TR002345 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. This publication is solely the responsibility of the authors and does not necessarily represent the official view of NCRR or NIH. Funding Information: This study was supported by the Lloyd J. Old Cancer Research Institute STAR Award (GP Dunn, Co-PI). Publisher Copyright: {\textcopyright} 2022, The Author(s).",
year = "2022",
month = dec,
doi = "10.1186/s13073-022-01051-9",
language = "English",
volume = "14",
journal = "Genome Medicine",
issn = "1756-994X",
number = "1",
}