Defining Phenotypic and Functional Heterogeneity of Glioblastoma Stem Cells by Mass Cytometry

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2021 Jan 5

PMID 33400685

Citations 13

Authors

Luciano Galdieri

Arijita Jash

Olga Malkova

Diane D Mao

Patrick DeSouza

Yunli E Chu

Amber Salter

Jian L Campian

Kristen M Naegle

Cameron W Brennan

Hiroaki Wakimoto

Stephen T Oh

Albert H Kim

Milan G Chheda

Affiliations

Soon will be listed here.

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.

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