@article{f1ccbba83640463a9aa81305ee69fdd8,
title = "Defining phenotypic and functional heterogeneity of glioblastoma stem cells by mass cytometry",
abstract = "Most patients with glioblastoma (GBM) die within 2 years. A major therapeutic goal is to target GBM stem cells (GSCs), a subpopulation of cells that contribute to treatment resistance and recurrence. Since their discovery in 2003, GSCs have been isolated using single-surface markers, such as CD15, CD44, CD133, and α6 integrin. It remains unknown how these single-surface marker-defined GSC populations compare with each other in terms of signaling and function and whether expression of different combinations of these markers is associated with different functional capacity. Using mass cytometry and fresh operating room specimens, we found 15 distinct GSC subpopulations in patients, and they differed in their MEK/ERK, WNT, and AKT pathway activation status. Once in culture, some subpopulations were lost and previously undetectable ones materialized. GSCs that highly expressed all 4 surface markers had the greatest self-renewal capacity, WNT inhibitor sensitivity, and in vivo tumorigenicity. This work highlights the potential signaling and phenotypic diversity of GSCs. Larger patient sample sizes and antibody panels are required to confirm these findings.",
author = "Luciano Galdieri and Arijita Jash and Olga Malkova and Mao, {Diane D.} and Patrick DeSouza and Chu, {Yunli E.} and Amber Salter and Campian, {Jian L.} and Naegle, {Kristen M.} and Brennan, {Cameron W.} and Hiroaki Wakimoto and Oh, {Stephen T.} and Kim, {Albert H.} and Chheda, {Milan G.}",
note = "Funding Information: reports research support from NeoImmuneTech Inc. and Incyte Corporation. AHK is a consultant for Monteris Medical and has a Stryker research grant, Monteris Medical research grant, and Collagen Matrix research grant. MGC reports research support from Orbus Therapeutics and royalties from UpToDate. The laboratory of MGC receives research support from NeoimmuneTech Inc. Funding Information: Research reported in this publication was supported by National Institute of Neurological Disorders and Stroke of NIH under award numbers R01 NS107833 and R01 NS117149 (to MGC) and R01 NS106612 (to AHK). Support for this work also came from the Doris Duke Charitable Foundation, Elsa U. Pardee Foundation, the Concern Foundation, the Cancer Research Foundation, and the McDonnell Center for Cellular and Molecular Neurobiology of Washington University (awarded to MGC). Additionally, research reported in this publication was supported by the Clinical and Translational Research Funding Program (to MGC) of the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of NIH and The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine (awarded to MGC). This research was supported by the Alvin J. Siteman Cancer Center Siteman Investment Program through funding from The Foundation for Barnes-Jewish Hospital and the Barnard Trust. Technical support was provided by the Immunomonitoring Laboratory, which is supported by the Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs and by National Cancer Institute Cancer Center Support grant P30CA91842. The content is solely the responsibility of the authors and does not necessarily represent the official views of NIH. Publisher Copyright: {\textcopyright} 2021, Galdieri et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.",
year = "2021",
month = feb,
day = "22",
doi = "10.1172/jci.insight.128456",
language = "English (US)",
volume = "6",
journal = "JCI insight",
issn = "2379-3708",
publisher = "The American Society for Clinical Investigation",
number = "4",
}