Defining phenotypic and functional heterogeneity of glioblastoma stem cells by mass cytometry
Open Access
- 5 January 2021
- journal article
- research article
- Published by American Society for Clinical Investigation in JCI Insight
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.Funding Information
- National Institute of Neurological Disorders and Stroke of the National Institutes of Health (R01 NS107833)
- National Institute of Neurological Disorders and Stroke of the National Institutes of Health (R01 NS094670)
- National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR002345)
- NCI Cancer Center (P30CA91842)
- The Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine (N/A)
- Doris Duke Charitable Foundation (N/A)
- Elsa U. Pardee Foundation (N/A)
- Concern Foundation (N/A)
- The Cancer Research Foundation (N/A)
- McDonnell Center for Cellular and Molecular Neurobiology of Washington University (N/A)
- National Institutes of Neurological Disorders and Stroke of the National Institutes of Health (R01 NS117149)
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