PDF(Pubmed)
Abstract：
UNASSIGNED: Glioma, a prevalent and deadly brain tumor, is marked by significant cellular heterogeneity and metabolic alterations. However, the comprehensive cell-of-origin and metabolic landscape in high-grade (Glioblastoma Multiforme, WHO grade IV) and low-grade (Oligoastrocytoma, WHO grade II) gliomas remains elusive.
UNASSIGNED: In this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas.
UNASSIGNED: Notably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance.
UNASSIGNED: Crucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression.
UNASSIGNED: In this study, we undertook single-cell transcriptome sequencing of these glioma grades to elucidate their cellular and metabolic distinctions. Following the identification of cell types, we compared metabolic pathway activities and gene expressions between high-grade and low-grade gliomas.
UNASSIGNED: Notably, astrocytes and oligodendrocyte progenitor cells (OPCs) exhibited the most substantial differences in both metabolic pathways and gene expression, indicative of their distinct origins. The comprehensive analysis identified the most altered metabolic pathways (MCPs) and genes across all cell types, which were further validated against TCGA and CGGA datasets for clinical relevance.
UNASSIGNED: Crucially, the metabolic enzyme phosphodiesterase 8B (PDE8B) was found to be exclusively expressed and progressively downregulated in astrocytes and OPCs in higher-grade gliomas. This decreased expression identifies PDE8B as a metabolism-related oncogene in IDH-mutant glioma, marking its dual role as both a protective marker for glioma grading and prognosis and as a facilitator in glioma progression.
摘要：
■胶质瘤，一种普遍而致命的脑瘤，以显著的细胞异质性和代谢改变为标志。然而,高级细胞的起源和代谢综合景观(多形性胶质母细胞瘤，WHOIV级)和低级别(寡星形细胞瘤，WHOII级）神经胶质瘤仍然难以捉摸。
■在这项研究中，我们对这些胶质瘤级别进行了单细胞转录组测序,以阐明它们的细胞和代谢差异.在确定细胞类型之后,我们比较了高级别和低级别胶质瘤的代谢途径活性和基因表达。
■值得注意的是，星形胶质细胞和少突胶质细胞祖细胞（OPCs）在代谢途径和基因表达方面表现出最实质性的差异，表明了它们不同的起源。综合分析确定了所有细胞类型中变化最大的代谢途径（MCP）和基因，针对TCGA和CGGA数据集进一步验证了其临床相关性。
■至关重要的是，发现代谢酶磷酸二酯酶8B(PDE8B)在高级别神经胶质瘤的星形胶质细胞和OPCs中仅表达并逐渐下调.这种降低的表达将PDE8B鉴定为IDH突变型神经胶质瘤中的代谢相关癌基因，标记其作为神经胶质瘤分级和预后的保护性标记和作为神经胶质瘤进展的促进者的双重作用。
■在这项研究中，我们对这些胶质瘤级别进行了单细胞转录组测序,以阐明它们的细胞和代谢差异.在确定细胞类型之后,我们比较了高级别和低级别胶质瘤的代谢途径活性和基因表达。
■值得注意的是，星形胶质细胞和少突胶质细胞祖细胞（OPCs）在代谢途径和基因表达方面表现出最实质性的差异，表明了它们不同的起源。综合分析确定了所有细胞类型中变化最大的代谢途径（MCP）和基因，针对TCGA和CGGA数据集进一步验证了其临床相关性。
■至关重要的是，发现代谢酶磷酸二酯酶8B(PDE8B)在高级别神经胶质瘤的星形胶质细胞和OPCs中仅表达并逐渐下调.这种降低的表达将PDE8B鉴定为IDH突变型神经胶质瘤中的代谢相关癌基因，标记其作为神经胶质瘤分级和预后的保护性标记和作为神经胶质瘤进展的促进者的双重作用。
