Dataset Information

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA-Seq.

ABSTRACT: High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation (SULT1E1⁺ ) in high-grade meningiomas. This subpopulation modulates the polarization of M2-type macrophages and promotes meningioma progression and recurrence. A novel patient-derived meningioma organoid (MO) model is established to characterize this unique subpopulation. The resulting MOs fully retain the aggressiveness of SULT1E1⁺ and exhibit invasiveness in the brain after orthotopic transplantation. By targeting SULT1E1⁺ in MOs, the synthetic compound SRT1720 is identified as a potential agent for systemic treatment and radiation sensitization. These findings shed light on the mechanism underlying the malignancy of high-grade meningiomas and provide a novel therapeutic target for refractory high-grade meningioma.

SUBMITTER: Huang M

PROVIDER: S-EPMC10214266 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature

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Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA-Seq.

Huang Meng M Xu Shao S Li Yuzhe Y Shang Li L Zhan Xiudan X Qin Chaoyin C Su Jun J Zhao Zijin Z He Yi Y Qin Lina L Zhao Wei W Long Wenyong W Liu Qing Q

Advanced science (Weinheim, Baden-Wurttemberg, Germany) 20230330 15

High-grade meningioma has an unsatisfactory outcome despite surgery and postoperative radiotherapy; however, the factors driving its malignancy and recurrence remain largely unknown, which limits the development of systemic treatments. Single-cell RNA sequencing (scRNA-Seq) technology is a powerful tool for studying intratumoral cellular heterogeneity and revealing the roles of various cell types in oncogenesis. In this study, scRNA-Seq is used to identify a unique initiating cell subpopulation ...[more]

PMID: 36994665

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Project description:BackgroundUlcerative colitis is a chronic inflammatory disease affecting the colon. During chronic inflammation of epithelial cells, lipid metabolism via pro-inflammatory eicosanoids is known to modify the immune response.MethodsStarting from the Mammalian Metabolic Database, the expression of metabolic enzymes was investigated in two independent cohorts from transcriptome datasets GSE38713 and GSE11223, which analyzed ulcerative colitis tissue samples from the digestive tract.ResultsIn the first cohort, 145 differentially expressed enzymes were identified as significantly regulated between ulcerative colitis tissues and normal controls. Overexpressed enzymes were selected to tune an Elastic Net model in the second cohort. Using the best parameters, the model achieved a prediction accuracy for ulcerative colitis with an area under the curve (AUC) of 0.79. Twenty-two metabolic enzymes were found to be commonly overexpressed in both independent cohorts, with decreasing Elastic Net predictive coefficients as follows: LIPG (3.98), PSAT1 (3.69), PGM3 (2.74), CD38 (2.28), BLVRA (1.99), CBR3 (1.94), NT5DC2 (1.76), PHGDH (1.71), GPX7 (1.58), CASP1 (1.56), ASRGL1 (1.4), SOD3 (1.25), CHST2 (0.965), CHST11 (0.95), KYNU (0.94), PLAG2G7 (0.92), SRM (0.87), PTGS2 (0.80), LPIN1 (0.47), ME1 (0.31), PTGDS (0.14), and ADA (0.13). Functional enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database highlighted the main implications of these enzymes in cysteine and methionine metabolism (adjusted p-value = 0.01), arachidonic acid and prostaglandin metabolism (adjusted p-value = 0.01), and carbon metabolism (adjusted p-value = 0.04). A metabolic score based on the transcriptional activation of the validated twenty-two enzymes was found to be significantly greater in Ulcerative colitis samples compared to healthy donor samples (p-value = 1.52 × 10-8).ConclusionsA metabolic expression score was established and reflects the implications of heterogeneous metabolic pathway deregulations in the digestive tract of patients with ulcerative colitis.

Dataset Information

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA-Seq.

Publications

Novel Human Meningioma Organoids Recapitulate the Aggressiveness of the Initiating Cell Subpopulations Identified by ScRNA-Seq.

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