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

Haddock, Sara; Alban, Tyler J.; Turcan, Şevin; Husic, Hana; Rosiek, Eric; Ma, Xiaoxiao; Wang, Yuxiang; Bale, Tejus; Makarov, Vladimir; Monette, Sébastien; Wu, Wei; Gardner, Rui; Manova, Katia; Boire, Adrienne; Chan, Timothy A.

doi:10.1016/j.neo.2022.100790

Cited by 11 publications

(10 citation statements)

References 75 publications

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“…GSCs from IDH-wild type glioblastomas are characterized to express PTPRZ1 6 , Sox2 and Nanog 13 , CD9, PROM1 (CD133), PDGFRA and OLIG2 14 . Proliferative cell population from IDH-mutant gliomas has neural progenitor cell-like profile expressing CD24 5 , 15 . However, there is no characterization of GSC population from IDH - and TP53 -mutant gliomas, therefore we still lack a systematic understanding of the driver mutation impact on the GSC fate, differentiation status and plasticity.…”

Section: Introductionmentioning

confidence: 99%

Single-nucleus transcriptomics of IDH1- and TP53-mutant glioma stem cells displays diversified commitment on invasive cancer progenitors

Gulaia

Shmelev

Romanishin

et al. 2022

Sci Rep

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Glioma is a devastating brain tumor with a high mortality rate attributed to the glioma stem cells (GSCs) possessing high plasticity. Marker mutations in isocitrate dehydrogenase type 1 (IDH1) and tumor protein 53 (TP53) are frequent in gliomas and impact the cell fate decisions. Understanding the GSC heterogeneity within IDH1- and TP53- mutant tumors may elucidate possible treatment targets. Here, we performed single-nucleus transcriptomics of mutant and wild-type glioma samples sorted for Sox2 stem cell marker. For the first time the rare subpopulations of Sox2 + IDH1- and TP53-mutant GSCs were characterized. In general, GSCs contained the heterogeneity root subpopulation resembling active neural stem cells capable of asymmetric division to quiescent and transit amplifying cell branches. Specifically, double-mutant GSCs revealed the commitment on highly invasive oligodendrocyte- and astroglia-like progenitors. Additionally, double-mutant GSCs displayed upregulated markers of collagen synthesis, altered lipogenesis and high migration, while wild-type GSCs expressed genes related to ATP production. Wild-type GSC root population was highly heterogeneous and lacked the signature marker expression, thus glioblastoma treatment should emphasize on establishing differentiation protocol directed against residual GSCs. For the more differentiated IDH1- and TP53-mutant gliomas we suggest therapeutic targeting of migration molecules, such as CD44.

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Section: Introductionmentioning

confidence: 99%

Single-nucleus transcriptomics of IDH1- and TP53-mutant glioma stem cells displays diversified commitment on invasive cancer progenitors

Gulaia

Shmelev

Romanishin

et al. 2022

Sci Rep

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“…Hypoxia activates HIF, resulting in the upregulation of the “do not-eat-me” signal surface markers (CD24 and CD47) and vascular endothelial growth factor, which bind to FLT1 in liver cancer [ 79 ]. IDH mutation induced phenotypic reprogramming in glioma, resulting in the generation of CSCs and an increase in CD24-positive cells [ 80 , 81 ].…”

Section: Resultsmentioning

confidence: 99%

Genetic heterogeneity of liver cancer stem cells

Kim

et al. 2022

Anat Cell Biol

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Cancer cell heterogeneity is a serious problem in the control of tumor progression because it can cause chemoresistance and metastasis. Heterogeneity can be generated by various mechanisms, including genetic evolution of cancer cells, cancer stem cells (CSCs), and niche heterogeneity. Because the genetic heterogeneity of CSCs has been poorly characterized, the genetic mutation status of CSCs was examined using Exome-Seq and RNA-Seq data of liver cancer.Here we show that different surface markers for liver cancer stem cells (LCSCs) showed a unique propensity for genetic mutations. Cluster of differentiation 133 (CD133)-positive cells showed frequent mutations in the IRF2, BAP1, and ERBB3 genes. However, leucine-rich repeat-containing G protein-coupled receptor 5-positive cells showed frequent mutations in the CTNNB1, RELN, and ROBO1 genes. In addition, some genetic mutations were frequently observed irrespective of the surface markers for LCSCs. BAP1 mutations was frequently observed in CD133-, CD24-, CD13-, CD90-, epithelial cell adhesion molecule-, or keratin 19-positive LCSCs. ASXL2, ERBB3, IRF2, TLX3, CPS1, and NFATC2 mutations were observed in more than three types of LCSCs, suggesting that common mechanisms for the development of these LCSCs. The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.

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“…Meanwhile, implanting BT054 cells into immunocompromised mice has not established reliable xenografts, limiting the utility of this model for in vivo studies of glioma biology ( 20 ). Notably, Rohle and colleagues generated an oligodendroglioma GSC line, TS603, that displays 1p/19q loss, harbors an endogenous, heterozygous IDH1 R132H mutation, and reliably forms subcutaneous and intracranial xenografts ( 21 , 22 ). Therefore, this constitutes a powerful model for studying LGG biology both in vitro and in vivo .…”

Section: Lgg Cell Linesmentioning

confidence: 99%

Preclinical modeling of lower-grade gliomas

et al. 2023

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Models for human gliomas prove critical not only to advancing our understanding of glioma biology but also to facilitate the development of therapeutic modalities. Specifically, creating lower-grade glioma (LGG) models has been challenging, contributing to few investigations and the minimal progress in standard treatment over the past decade. In order to reliably predict and validate the efficacies of novel treatments, however, LGG models need to adhere to specific standards that recapitulate tumor genetic aberrations and micro-environment. This underscores the need to revisit existing models of LGG and explore prospective models that may bridge the gap between preclinical insights and clinical translation. This review first outlines a set of criteria aimed to address the current challenges hindering model development. We then evaluate the strengths and weaknesses of existing preclinical models of LGG with respect to these established standards. To conclude, the review discusses potential future directions for integrating existing models to maximize the exploration of disease mechanisms and therapeutics development.

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

Cited by 11 publications

References 75 publications

Single-nucleus transcriptomics of IDH1- and TP53-mutant glioma stem cells displays diversified commitment on invasive cancer progenitors

Single-nucleus transcriptomics of IDH1- and TP53-mutant glioma stem cells displays diversified commitment on invasive cancer progenitors

Genetic heterogeneity of liver cancer stem cells

Preclinical modeling of lower-grade gliomas

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