Integration of single-cell and bulk RNA sequencing data reveals key cell types and regulators in traumatic brain injury

Rui-zhe Zheng; Jin Xing; Qiong Huang; Xi-tao Yang; Chang-yi Zhao; Xin-yuan Li; Rui-zhe Zheng; Jin Xing; Qiong Huang; Xi-tao Yang; Chang-yi Zhao; Xin-yuan Li

doi:10.3934/mbe.2021065

Mathematical Biosciences and Engineering

2021, Volume 18, Issue 2: 1201-1214. doi: 10.3934/mbe.2021065

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Integration of single-cell and bulk RNA sequencing data reveals key cell types and regulators in traumatic brain injury

1.
Department of Neurosurgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
2.
Department of Neurosurgery, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China
3.
Department of Neurology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200336, China
4.
Department of Neurosurgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
† These authors contributed equally to this work

Received: 12 October 2020 Accepted: 10 January 2021 Published: 14 January 2021

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide, whose symptoms ranging from mild to severe, even life-threatening. However, specific cell types and key regulators involved in traumatic brain injury have not been well elucidated. In this study, utilizing single-cell RNA-seq (scRNA-seq) data from mice with TBI, we have successfully identified and characterized 13 cell populations including astrocytes, oligodendrocyte, newly formed oligodendrocytes, microglia, two types of endothelial cells, five types of excitatory and two types of inhibitory neurons. Differential expression analysis and gene set enrichment analysis (GSEA) revealed the upregulation of microglia and endothelial markers, along with the downregulation of markers of excitatory neurons in TBI. The cell-cell communication analysis revealed that microglia and endothelial cell might interact through the interaction of Icam1-Il2rg and C1qa-Cd93, and microglia might also communicate with each other via Icam1-Itagm. The autocrine ligand-receptor in microglia might result in activation of TYROBP causal network via Icam1-Itgam. The cell-cell contact between microglia and endothelial cell might activate integrin signaling pathways. Moreover, we also found that genes involved in microglia activation were highly downregulated in Tyrobp/Dap12-deficient microglia, indicating that the upregulation of Tyrobp and TYROBP causal network in microglia might be a candidate therapeutic target in TBI. In contrast, the excitatory neurons were involved in maintaining normal brain function, and their inactivation might cause dysfunction of nervous system in TBI patients. In conclusion, the present study has discerned major cell types such as microglia, endothelial cells and excitatory neurons, and revealed key regulator such as TYROBP, C1QA, and CD93 in TBI, which shall improve our understanding of the pathogenesis of TBI.
- traumatic brain injury,
- single-cell RNA-seq,
- cell-cell communication,
- TYROBP causal network,
- microglia
Citation: Rui-zhe Zheng, Jin Xing, Qiong Huang, Xi-tao Yang, Chang-yi Zhao, Xin-yuan Li. Integration of single-cell and bulk RNA sequencing data reveals key cell types and regulators in traumatic brain injury[J]. Mathematical Biosciences and Engineering, 2021, 18(2): 1201-1214. doi: 10.3934/mbe.2021065

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Abstract

Traumatic brain injury (TBI) is a leading cause of disability and mortality worldwide, whose symptoms ranging from mild to severe, even life-threatening. However, specific cell types and key regulators involved in traumatic brain injury have not been well elucidated. In this study, utilizing single-cell RNA-seq (scRNA-seq) data from mice with TBI, we have successfully identified and characterized 13 cell populations including astrocytes, oligodendrocyte, newly formed oligodendrocytes, microglia, two types of endothelial cells, five types of excitatory and two types of inhibitory neurons. Differential expression analysis and gene set enrichment analysis (GSEA) revealed the upregulation of microglia and endothelial markers, along with the downregulation of markers of excitatory neurons in TBI. The cell-cell communication analysis revealed that microglia and endothelial cell might interact through the interaction of Icam1-Il2rg and C1qa-Cd93, and microglia might also communicate with each other via Icam1-Itagm. The autocrine ligand-receptor in microglia might result in activation of TYROBP causal network via Icam1-Itgam. The cell-cell contact between microglia and endothelial cell might activate integrin signaling pathways. Moreover, we also found that genes involved in microglia activation were highly downregulated in Tyrobp/Dap12-deficient microglia, indicating that the upregulation of Tyrobp and TYROBP causal network in microglia might be a candidate therapeutic target in TBI. In contrast, the excitatory neurons were involved in maintaining normal brain function, and their inactivation might cause dysfunction of nervous system in TBI patients. In conclusion, the present study has discerned major cell types such as microglia, endothelial cells and excitatory neurons, and revealed key regulator such as TYROBP, C1QA, and CD93 in TBI, which shall improve our understanding of the pathogenesis of TBI.

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