神经胶质瘤是一种普遍且致命的脑肿瘤，其特点是显着的细胞异质性和代谢改变。然而，高级别（多形性胶质母细胞瘤，WHO IV 级）和低级别（少星形细胞瘤，WHO II 级）神经胶质瘤的综合细胞起源和代谢状况仍然难以捉摸。在这项研究中，我们进行了单细胞转录组测序这些神经胶质瘤分级以阐明它们的细胞和代谢差异。在鉴定细胞类型后，我们比较了高级别和低级别胶质瘤之间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（OPC）在代谢途径和基因表达方面表现出最显着的差异，表明他们独特的起源。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，并根据 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) 是唯一表达的，并且逐渐发展高级神经胶质瘤中星形胶质细胞和 OPC 下调。这种表达减少表明 PDE8B 是 IDH 突变神经胶质瘤中与代谢相关的癌基因，标志着其双重作用，既作为神经胶质瘤分级和预后的保护性标记物，又作为神经胶质瘤进展的促进剂。版权所有 © 2024 He, Peng, Wang, Yang,周、龚、宋、王。

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.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.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.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.Copyright © 2024 He, Peng, Wang, Yang, Zhou, Gong, Song and Wang.