Spatial metabolic heterogeneity of oligodendrogliomas at single-cell resolution.

IF 2.7 3区 医学 Q2 CLINICAL NEUROLOGY Brain Tumor Pathology Pub Date : 2023-04-01 DOI:10.1007/s10014-023-00455-8
Sai Batchu, Michael Joseph Diaz, Giona Kleinberg, Brandon Lucke-Wold
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引用次数: 1

Abstract

Oligodendrogliomas are a type of rare and incurable gliomas whose metabolic profiles have yet to be fully examined. The present study examined the spatial differences in metabolic landscapes underlying oligodendrogliomas and should provide unique insights into the metabolic characteristics of these uncommon tumors. Single-cell RNA-sequencing expression profiles from 4044 oligodendroglioma cells derived from tumors resected from four locations frontal, temporal, parietal, and frontotemporoinsular) and in which 1p/19q co-deletion and IDH1 or IDH2 mutations were confirmed were computationally analyzed through a robust workflow to elucidate relative differences in metabolic pathway activities among the different locations. Dimensionality reduction using metabolic expression profiles exhibited clustering corresponding to each location subgroup. From the 80 metabolic pathways examined, over 70 pathways had significantly different activity scores between location subgroups. Further analysis of metabolic heterogeneity suggests that mitochondrial oxidative phosphorylation accounts for considerable metabolic variation within the same locations. Steroid and fatty acid metabolism pathways were also found to be major contributors to heterogeneity. Oligodendrogliomas display distinct spatial metabolic differences in addition to intra-location metabolic heterogeneity.

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单细胞分辨率下少突胶质细胞瘤的空间代谢异质性。
少突胶质细胞瘤是一种罕见且无法治愈的胶质瘤,其代谢谱尚未得到充分的研究。本研究考察了少突胶质细胞瘤代谢景观的空间差异,并为这些罕见肿瘤的代谢特征提供了独特的见解。通过一个强大的工作流计算分析了4044个少突胶质细胞的单细胞rna测序表达谱,这些细胞来自四个位置切除的肿瘤,分别来自额叶、颞叶、顶叶和额颞叶),其中1p/19q共缺失和IDH1或IDH2突变被证实,以阐明不同位置之间代谢途径活性的相对差异。利用代谢表达谱进行降维,显示出对应于每个位置亚组的聚类。在研究的80条代谢途径中,超过70条途径在不同位置亚组之间具有显著不同的活动得分。对代谢异质性的进一步分析表明,线粒体氧化磷酸化在相同位置内造成了相当大的代谢差异。类固醇和脂肪酸代谢途径也被发现是异质性的主要贡献者。少突胶质细胞瘤除了表现出位置内代谢异质性外,还表现出明显的空间代谢差异。
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来源期刊
Brain Tumor Pathology
Brain Tumor Pathology 医学-病理学
CiteScore
5.40
自引率
9.10%
发文量
30
审稿时长
>12 weeks
期刊介绍: Brain Tumor Pathology is the official journal of the Japan Society of Brain Tumor Pathology. This international journal documents the latest research and topical debate in all clinical and experimental fields relating to brain tumors, especially brain tumor pathology. The journal has been published since 1983 and has been recognized worldwide as a unique journal of high quality. The journal welcomes the submission of manuscripts from any country. Membership in the society is not a prerequisite for submission. The journal publishes original articles, case reports, rapid short communications, instructional lectures, review articles, letters to the editor, and topics.Review articles and Topics may be recommended at the annual meeting of the Japan Society of Brain Tumor Pathology. All contributions should be aimed at promoting international scientific collaboration.
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