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整合空间转录组和代谢组研究揭示人类损伤大脑中的代谢异质性。

Integrated spatial transcriptome and metabolism study reveals metabolic heterogeneity in human injured brain.

机构信息

Department of Neurosurgery, Shanghai Pudong New Area People's Hospital, Shanghai, China; Key Laboratory, Shanghai Pudong New Area People's Hospital, Shanghai, China.

Department of Neurosurgery, Shanghai Fengxian District Central Hospital, Shanghai Jiaotong University Affiliated Sixth People's Hospital South Campus, Shanghai, China.

出版信息

Cell Rep Med. 2023 Jun 20;4(6):101057. doi: 10.1016/j.xcrm.2023.101057. Epub 2023 May 31.

DOI:10.1016/j.xcrm.2023.101057
PMID:37263268
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10313933/
Abstract

Single-cell transcriptomics can provide quantitative molecular signatures for large, unbiased samples of the diverse cell types in the brain. With the advances of multi-omics datasets, a major challenge is to validate and integrate results into a biological understanding of spatial organization and functional orientation. Here, we generate spatial transcriptomes and metabolites from six patients with brain trauma with surgical samples. The resulting spatial marker gene, which is highly replicable across analysis methods, sequencing technologies, and modalities, is a comprehensive molecular marker of the diverse metabolic changes in human injured brains. The atlas includes an area of lipid peroxidation that resembles injured neurons in the brain. We further discover imbalanced myo-inositol and myo-inositol phosphate and related spatial markers. Our results highlight the complex transcriptomic regulation and metabolic alterations in the injured brain and will directly enable the design of reagents to target specific genes in the human brain for functional analysis.

摘要

单细胞转录组学可以为大脑中多样化细胞类型的大、无偏样本提供定量分子特征。随着多组学数据集的进步,一个主要挑战是验证和整合结果,以了解空间组织和功能定向的生物学。在这里,我们从六名脑外伤患者的手术样本中生成空间转录组和代谢物。由此产生的空间标记基因在分析方法、测序技术和模式上具有高度可复制性,是人类损伤大脑中多种代谢变化的综合分子标记。图谱包括一个脂质过氧化区域,类似于大脑中的损伤神经元。我们进一步发现肌醇和肌醇磷酸盐的不平衡以及相关的空间标记物。我们的结果强调了损伤大脑中复杂的转录组调控和代谢变化,并将直接使试剂设计能够针对人类大脑中的特定基因进行功能分析。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/495f963c1df0/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/4c06993c7109/fx1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/9668bb8532af/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/a5083802f09a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/6ef7d757bab4/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/a4ed538c3c07/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/555d1994ada5/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/495f963c1df0/gr7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/4c06993c7109/fx1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/da7372bf6ea7/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/9668bb8532af/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/a5083802f09a/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/6ef7d757bab4/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/a4ed538c3c07/gr5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/555d1994ada5/gr6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/875b/10313933/495f963c1df0/gr7.jpg

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