Xing Jin, Ren Li, Xu Hao, Zhao Liang, Wang Zhi-Han, Hu Guang-Dong, Wei Zi-Long
Department of Neurosurgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.
Front Genet. 2022 Jun 30;13:861428. doi: 10.3389/fgene.2022.861428. eCollection 2022.
Traumatic brain injury (TBI) is currently a substantial public health problem and one of the leading causes of morbidity and mortality worldwide. However, the cellular and transcriptional changes in TBI at single-cell level have not been well characterized. In this study, we reanalyzed a single-cell RNA sequencing (scRNA-seq) dataset of mouse hippocampus to identify the key cellular and transcriptional changes associated with TBI. Specifically, we found that oligodendrocytes were the most abundant cell type in mouse hippocampus, and detected an expanded astrocyte population, which was significantly activated in TBI. The enhanced activity of inflammatory response-related pathways in the astrocytes of TBI samples suggested that the astrocytes, along with microglia, which were the major brain-resident immune cells, were responsible for inflammation in the acute phase of TBI. Hormone secretion, transport, and exocytosis were found upregulated in the excitatory neurons of TBI, which gave us a hint that excitatory neurons might excessively transport and excrete glutamate in response to TBI. Moreover, the ependymal subpopulation C0 was TBI-specific and characterized by downregulated cilium movement, indicating that the attenuated activity of cilium movement following TBI might decrease cerebrospinal fluid flow. Furthermore, we observed that downregulated genes in response to candesartan treatment were preferentially expressed in excitatory neurons and were related to pathways like neuronal systems and neuroactive ligand-receptor interaction, indicating that candesartan might promote recovery of neurons after traumatic brain injury mediating neuroactive ligand-receptor interactions and reducing excitotoxicity. In conclusion, our study identified key cell types in TBI, which improved our understanding of the cellular and transcriptional changes after TBI and offered an insight into the molecular mechanisms that could serve as therapeutic targets.
创伤性脑损伤（TBI）目前是一个严重的公共卫生问题，也是全球发病和死亡的主要原因之一。然而，TBI在单细胞水平上的细胞和转录变化尚未得到充分表征。在本研究中，我们重新分析了小鼠海马体的单细胞RNA测序（scRNA-seq）数据集，以确定与TBI相关的关键细胞和转录变化。具体而言，我们发现少突胶质细胞是小鼠海马体中最丰富的细胞类型，并检测到星形胶质细胞群体扩大，其在TBI中显著激活。TBI样本中星形胶质细胞中炎症反应相关通路的活性增强表明，星形胶质细胞与作为主要脑内驻留免疫细胞的小胶质细胞一起，在TBI急性期负责炎症反应。在TBI的兴奋性神经元中发现激素分泌、转运和胞吐作用上调，这提示我们兴奋性神经元可能在TBI时过度转运和分泌谷氨酸。此外，室管膜亚群C0是TBI特异性的，其特征是纤毛运动下调，这表明TBI后纤毛运动活性减弱可能会减少脑脊液流动。此外，我们观察到坎地沙坦治疗后下调的基因优先在兴奋性神经元中表达，并且与神经元系统和神经活性配体-受体相互作用等通路相关，这表明坎地沙坦可能通过介导神经活性配体-受体相互作用和降低兴奋性毒性来促进创伤性脑损伤后神经元的恢复。总之，我们的研究确定了TBI中的关键细胞类型，这加深了我们对TBI后细胞和转录变化的理解，并为可作为治疗靶点的分子机制提供了见解。
