Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
NHC Key Laboratory of Prevention and treatment of Cerebrovascular Diseases, Zhengzhou, China.
Sci Data. 2023 Sep 29;10(1):666. doi: 10.1038/s41597-023-02512-5.
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.
由于代谢失调是中风和阿尔茨海默病（AD）的共同特征，因此挖掘这些疾病中的共同代谢模式将有助于确定其可能的发病机制和潜在的干预靶点。然而，目前仍缺乏对这些疾病代谢网络的系统综合分析。在这项研究中，我们整合了缺血性中风（IS）、出血性中风（HS）和 AD 模型的单细胞 RNA 测序数据集，以构建单细胞水平的代谢通量图谱。我们发现，这三种疾病会导致内皮细胞的共同代谢变化。这些改变的代谢模块主要富集在转运体相关途径中，并预测可能导致代谢物如丙酮酸和延胡索酸的减少。我们进一步发现，Lef1、Elk3 和 Fosl1 可能是引起代谢变化的上游转录调节因子，可能是阻止神经退行性进程的干预措施的潜在靶点。
