Characterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis
The detailed characteristics of neuronal cell populations in Alzheimer’s disease (AD) using single-cell RNA sequencing have not been fully elucidated. To explore the characterization of neuronal cell populations in AD, this study utilized the publicly available single-nucleus RNA-sequencing datasets...
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Frontiers Media S.A.
2021
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oai:doaj.org-article:362da5a7d68c4f7fa15e515b29a5fa322021-11-08T06:40:45ZCharacterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis1663-436510.3389/fnagi.2021.742176https://doaj.org/article/362da5a7d68c4f7fa15e515b29a5fa322021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fnagi.2021.742176/fullhttps://doaj.org/toc/1663-4365The detailed characteristics of neuronal cell populations in Alzheimer’s disease (AD) using single-cell RNA sequencing have not been fully elucidated. To explore the characterization of neuronal cell populations in AD, this study utilized the publicly available single-nucleus RNA-sequencing datasets in the transgenic model of 5X familial Alzheimer’s disease (5XFAD) and wild-type mice to reveal an AD-associated excitatory neuron population (C3:Ex.Neuron). The relative abundance of C3:Ex.Neuron increased at 1.5 months and peaked at 4.7 months in AD mice. Functional pathways analyses showed that the pathways positively related to neurodegenerative disease progression were downregulated in the C3:Ex.Neuron at 1.5 months in AD mice. Based on the differentially expressed genes among the C3:Ex.Neuron, four subtypes (C3.1–4) were identified, which exhibited distinct abundance regulatory patterns during the development of AD. Among these subtypes, the C3.1 neurons [marked by netrin G1 (Ntng1)] exhibited a similar regulatory pattern as the C3:Ex.Neuron in abundance during the development of AD. In addition, our gene set variation analysis (GSEA) showed that the C3.1 neurons, instead of other subtypes of the C3:Ex.Neuron, possessed downregulated AD pathways at an early stage (1.5 months) of AD mice. Collectively, our results identified a previously unidentified subset of excitatory neurons and provide a potential application of these neurons to modulate the disease susceptibility.Fanghong ShaoFanghong ShaoFanghong ShaoMeiting WangMeiting WangQi GuoQi GuoQi GuoBowen ZhangBowen ZhangBowen ZhangXiangting WangXiangting WangXiangting WangFrontiers Media S.A.articleAlzheimer’s diseasesingle-cell sequencing5XFAD miceexcitatory neuronsnetrin G1Neurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENFrontiers in Aging Neuroscience, Vol 13 (2021) |
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| topic |
Alzheimer’s disease single-cell sequencing 5XFAD mice excitatory neurons netrin G1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 |
| spellingShingle |
Alzheimer’s disease single-cell sequencing 5XFAD mice excitatory neurons netrin G1 Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Fanghong Shao Fanghong Shao Fanghong Shao Meiting Wang Meiting Wang Qi Guo Qi Guo Qi Guo Bowen Zhang Bowen Zhang Bowen Zhang Xiangting Wang Xiangting Wang Xiangting Wang Characterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis |
| description |
The detailed characteristics of neuronal cell populations in Alzheimer’s disease (AD) using single-cell RNA sequencing have not been fully elucidated. To explore the characterization of neuronal cell populations in AD, this study utilized the publicly available single-nucleus RNA-sequencing datasets in the transgenic model of 5X familial Alzheimer’s disease (5XFAD) and wild-type mice to reveal an AD-associated excitatory neuron population (C3:Ex.Neuron). The relative abundance of C3:Ex.Neuron increased at 1.5 months and peaked at 4.7 months in AD mice. Functional pathways analyses showed that the pathways positively related to neurodegenerative disease progression were downregulated in the C3:Ex.Neuron at 1.5 months in AD mice. Based on the differentially expressed genes among the C3:Ex.Neuron, four subtypes (C3.1–4) were identified, which exhibited distinct abundance regulatory patterns during the development of AD. Among these subtypes, the C3.1 neurons [marked by netrin G1 (Ntng1)] exhibited a similar regulatory pattern as the C3:Ex.Neuron in abundance during the development of AD. In addition, our gene set variation analysis (GSEA) showed that the C3.1 neurons, instead of other subtypes of the C3:Ex.Neuron, possessed downregulated AD pathways at an early stage (1.5 months) of AD mice. Collectively, our results identified a previously unidentified subset of excitatory neurons and provide a potential application of these neurons to modulate the disease susceptibility. |
| format |
article |
| author |
Fanghong Shao Fanghong Shao Fanghong Shao Meiting Wang Meiting Wang Qi Guo Qi Guo Qi Guo Bowen Zhang Bowen Zhang Bowen Zhang Xiangting Wang Xiangting Wang Xiangting Wang |
| author_facet |
Fanghong Shao Fanghong Shao Fanghong Shao Meiting Wang Meiting Wang Qi Guo Qi Guo Qi Guo Bowen Zhang Bowen Zhang Bowen Zhang Xiangting Wang Xiangting Wang Xiangting Wang |
| author_sort |
Fanghong Shao |
| title |
Characterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis |
| title_short |
Characterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis |
| title_full |
Characterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis |
| title_fullStr |
Characterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis |
| title_full_unstemmed |
Characterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis |
| title_sort |
characterization of alzheimer’s disease-associated excitatory neurons via single-cell rna sequencing analysis |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/362da5a7d68c4f7fa15e515b29a5fa32 |
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