The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity - Sorbonne Université Access content directly
Journal Articles Brain, Behavior, and Immunity Year : 2020

The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity

Abstract

Glioblastoma cell ability to adapt their functioning to microenvironment changes is a source of the extensive intratumor heterogeneity characteristic of this devastating malignant brain tumor. A systemic view of the metabolic pathways underlying glioblastoma cell functioning states is lacking. We analyzed public single cell RNA-sequencing data from glioblastoma surgical resections, which offer the closest available view of tumor cell heterogeneity as encountered at the time of patients' diagnosis. Unsupervised analyses revealed that information dispersed throughout the cell transcript repertoires encoded the identity of each tumor and masked information related to cell functioning states. Data reduction based on an experimentally-defined signature of transcription factors overcame this hurdle. It allowed cell grouping according to their tumorigenic potential, regardless of their tumor of origin. The approach relevance was validated using independent datasets of glioblastoma cell and tissue transcriptomes, patient-derived cell lines and orthotopic xenografts. Overexpression of genes coding for amino acid and lipid metabolism enzymes involved in anti-oxidative, energetic and cell membrane processes characterized cells with high tumorigenic potential. Modeling of their expression network highlighted the very long chain polyunsaturated fatty acid synthesis pathway at the core of the network. Expression of its most downstream enzymatic component, ELOVL2, was associated with worsened patient survival, and required for cell tumorigenic properties in vivo. Our results demonstrate the power of signature-driven analyses of single cell transcriptomes to obtain an integrated view of metabolic pathways at play within the heterogeneous cell landscape of patient tumors.

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Cancer
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hal-03941235 , version 1 (16-01-2023)

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Alessandra Bispo da Silva, Paulo Lucas Cerqueira Coelho, Mona das Neves Oliveira, Joana Luz Oliveira, Jéssika Alves Oliveira Amparo, et al.. The flavonoid rutin and its aglycone quercetin modulate the microglia inflammatory profile improving antiglioma activity. Brain, Behavior, and Immunity, 2020, 85, pp.170-185. ⟨10.1016/j.bbi.2019.05.003⟩. ⟨hal-03941235⟩
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