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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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Autores principales: Shao, Fanghong, Wang, Meiting, Guo, Qi, Zhang, Bowen, Wang, Xiangting
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606650/
https://www.ncbi.nlm.nih.gov/pubmed/34819847
http://dx.doi.org/10.3389/fnagi.2021.742176
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author Shao, Fanghong
Wang, Meiting
Guo, Qi
Zhang, Bowen
Wang, Xiangting
author_facet Shao, Fanghong
Wang, Meiting
Guo, Qi
Zhang, Bowen
Wang, Xiangting
author_sort Shao, Fanghong
collection PubMed
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.
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spelling pubmed-86066502021-11-23 Characterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis Shao, Fanghong Wang, Meiting Guo, Qi Zhang, Bowen Wang, Xiangting Front Aging Neurosci Neuroscience 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. Frontiers Media S.A. 2021-11-08 /pmc/articles/PMC8606650/ /pubmed/34819847 http://dx.doi.org/10.3389/fnagi.2021.742176 Text en Copyright © 2021 Shao, Wang, Guo, Zhang and Wang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Shao, Fanghong
Wang, Meiting
Guo, Qi
Zhang, Bowen
Wang, Xiangting
Characterization of Alzheimer’s Disease-Associated Excitatory Neurons via Single-Cell RNA Sequencing Analysis
title 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_short 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
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8606650/
https://www.ncbi.nlm.nih.gov/pubmed/34819847
http://dx.doi.org/10.3389/fnagi.2021.742176
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