Shared metabolic shifts in endothelial cells in stroke and Alzheimer’s disease revealed by integrated analysis
Abstract Since metabolic dysregulation is a hallmark of both stroke and Alzheimer’s disease (AD), mining shared metabolic patterns in these diseases will help to identify their possible pathogenic mechanisms and potential intervention targets. However, a systematic integration analysis of the metabo...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-09-01
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| Series: | Scientific Data |
| Online Access: | https://doi.org/10.1038/s41597-023-02512-5 |
| _version_ | 1827724718430486528 |
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| author | Guangyu Guo Liyuan Fan Yingxue Yan Yunhao Xu Zhifen Deng Miaomiao Tian Yaoqi Geng Zongping Xia Yuming Xu |
| author_facet | Guangyu Guo Liyuan Fan Yingxue Yan Yunhao Xu Zhifen Deng Miaomiao Tian Yaoqi Geng Zongping Xia Yuming Xu |
| author_sort | Guangyu Guo |
| collection | DOAJ |
| description | Abstract Since metabolic dysregulation is a hallmark of both stroke and Alzheimer’s disease (AD), mining shared metabolic patterns in these diseases will help to identify their possible pathogenic mechanisms and potential intervention targets. However, a systematic integration analysis of the metabolic networks of the these diseases is still lacking. In this study, we integrated single-cell RNA sequencing datasets of ischemic stroke (IS), hemorrhagic stroke (HS) and AD models to construct metabolic flux profiles at the single-cell level. We discovered that the three disorders cause shared metabolic shifts in endothelial cells. These altered metabolic modules were mainly enriched in the transporter-related pathways and were predicted to potentially lead to a decrease in metabolites such as pyruvate and fumarate. We further found that Lef1, Elk3 and Fosl1 may be upstream transcriptional regulators causing metabolic shifts and may be possible targets for interventions that halt the course of neurodegeneration. |
| first_indexed | 2024-03-10T22:20:28Z |
| format | Article |
| id | doaj.art-8f75c9bf916946aa8c493750b59e7c75 |
| institution | Directory Open Access Journal |
| issn | 2052-4463 |
| language | English |
| last_indexed | 2024-03-10T22:20:28Z |
| publishDate | 2023-09-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Data |
| spelling | doaj.art-8f75c9bf916946aa8c493750b59e7c752023-11-19T12:19:09ZengNature PortfolioScientific Data2052-44632023-09-0110111210.1038/s41597-023-02512-5Shared metabolic shifts in endothelial cells in stroke and Alzheimer’s disease revealed by integrated analysisGuangyu Guo0Liyuan Fan1Yingxue Yan2Yunhao Xu3Zhifen Deng4Miaomiao Tian5Yaoqi Geng6Zongping Xia7Yuming Xu8Department of Neurology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou UniversityClinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou UniversityClinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou UniversityClinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou UniversityClinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou UniversityClinical Systems Biology Laboratories, the First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou UniversityDepartment of Neurology, The First Affiliated Hospital of Zhengzhou UniversityAbstract Since metabolic dysregulation is a hallmark of both stroke and Alzheimer’s disease (AD), mining shared metabolic patterns in these diseases will help to identify their possible pathogenic mechanisms and potential intervention targets. However, a systematic integration analysis of the metabolic networks of the these diseases is still lacking. In this study, we integrated single-cell RNA sequencing datasets of ischemic stroke (IS), hemorrhagic stroke (HS) and AD models to construct metabolic flux profiles at the single-cell level. We discovered that the three disorders cause shared metabolic shifts in endothelial cells. These altered metabolic modules were mainly enriched in the transporter-related pathways and were predicted to potentially lead to a decrease in metabolites such as pyruvate and fumarate. We further found that Lef1, Elk3 and Fosl1 may be upstream transcriptional regulators causing metabolic shifts and may be possible targets for interventions that halt the course of neurodegeneration.https://doi.org/10.1038/s41597-023-02512-5 |
| spellingShingle | Guangyu Guo Liyuan Fan Yingxue Yan Yunhao Xu Zhifen Deng Miaomiao Tian Yaoqi Geng Zongping Xia Yuming Xu Shared metabolic shifts in endothelial cells in stroke and Alzheimer’s disease revealed by integrated analysis Scientific Data |
| title | Shared metabolic shifts in endothelial cells in stroke and Alzheimer’s disease revealed by integrated analysis |
| title_full | Shared metabolic shifts in endothelial cells in stroke and Alzheimer’s disease revealed by integrated analysis |
| title_fullStr | Shared metabolic shifts in endothelial cells in stroke and Alzheimer’s disease revealed by integrated analysis |
| title_full_unstemmed | Shared metabolic shifts in endothelial cells in stroke and Alzheimer’s disease revealed by integrated analysis |
| title_short | Shared metabolic shifts in endothelial cells in stroke and Alzheimer’s disease revealed by integrated analysis |
| title_sort | shared metabolic shifts in endothelial cells in stroke and alzheimer s disease revealed by integrated analysis |
| url | https://doi.org/10.1038/s41597-023-02512-5 |
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