Phenotypic and molecular states of IDH1 mutation-induced CD24-positive glioma stem-like cells

• Published in: Neoplasia (New York, N.Y.) Vol. 28; p. 100790
• Main Authors: Haddock, Sara, Alban, Tyler J., Turcan, Şevin, Husic, Hana, Rosiek, Eric, Ma, Xiaoxiao, Wang, Yuxiang, Bale, Tejus, Desrichard, Alexis, Makarov, Vladimir, Monette, Sebastien, Wu, Wei, Gardner, Rui, Manova, Katia, Boire, Adrienne, Chan, Timothy A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.06.2022; Neoplasia Press; Elsevier
• Subjects: Brain Neoplasms - genetics; Brain Neoplasms - metabolism; Brain Neoplasms - pathology; cancer stem cells; CD24; CD24 Antigen - genetics; CD24 Antigen - metabolism; Glioma - genetics; Glioma - metabolism; Glioma - pathology; Humans; IDH1 mutation; Isocitrate Dehydrogenase - genetics; Isocitrate Dehydrogenase - metabolism; Low-grade glioma; Mutation; Neoplastic Stem Cells - metabolism; Neoplastic Stem Cells - pathology; Neural stem cells; Original article; Orthotopic mouse model; Phenotype; hNSC; dox; IDH1 mutation; GBM; TERT; FDR; OE; NCBI; cancer stem cells; WHO; NSG; EGF; IDH1; MSKCC; qRT-PCR; GSEA; MSigDB; Orthotopic mouse model; LGG; RNAseq; bFGF; TCGA; Low-grade glioma; EdU; Neural stem cells; SEM; CD24; NTC; NES
• ISSN: 1476-5586; 1522-8002; 1476-5586
• DOI: 10.1016/j.neo.2022.100790

Mutations in IDH1 and IDH2 drive the development of gliomas. These genetic alterations promote tumor cell renewal, disrupt differentiation states, and induce stem-like properties. Understanding how this phenotypic reprogramming occurs remains an area of high interest in glioma research. Previously, we showed that IDH mutation results in the development of a CD24-positive cell population in gliomas. Here, we demonstrate that this CD24-positive population possesses striking stem-like properties at the molecular and phenotypic levels. We found that CD24 expression is associated with stem-like features in IDH-mutant tumors, a patient-derived gliomasphere model, and a neural stem cell model of IDH1-mutant glioma. In orthotopic models, CD24-positive cells display enhanced tumor initiating potency compared to CD24-negative cells. Furthermore, CD24 knockdown results in changes in cell viability, proliferation rate, and gene expression that closely resemble a CD24-negative phenotype. Our data demonstrate that induction of a CD24-positive population is one mechanism by which IDH-mutant tumors acquire stem-like properties. These findings have significant implications for our understanding of the molecular underpinnings of IDH-mutant gliomas.