Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s disease
Abstract Understanding the phenotypic and functional diversity of cerebral cortical GABAergic neurons requires a comprehensive analysis of key transcriptional signatures and neuronal subtype identity. However, the diversity and conservation of GABAergic neurons across multiple mammals remain unclear...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-11-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-21496-7 |
| _version_ | 1798018193278631936 |
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| author | Shiyou Wang Peiwen Ding Jingnan Yuan Haoyu Wang Xiuqing Zhang Dongsheng Chen Dongli Ma Xingliang Zhang Fei Wang |
| author_facet | Shiyou Wang Peiwen Ding Jingnan Yuan Haoyu Wang Xiuqing Zhang Dongsheng Chen Dongli Ma Xingliang Zhang Fei Wang |
| author_sort | Shiyou Wang |
| collection | DOAJ |
| description | Abstract Understanding the phenotypic and functional diversity of cerebral cortical GABAergic neurons requires a comprehensive analysis of key transcriptional signatures and neuronal subtype identity. However, the diversity and conservation of GABAergic neurons across multiple mammals remain unclear. Here, we collected the single-nucleus RNA sequencing (snRNA-seq) datasets of cerebral cortex from human, macaque, mouse, and pig to identify the conserved neuronal cell types across species. After systematic analysis of the heterogeneity of GABAergic neurons, we defined four major conserved GABAergic neuron subclasses (Inc SST, Inc LAMP5, Inc PVALB, and Inc VIP) across species. We characterized the species-enriched subclasses of GABAergic neurons from four mammals, such as Inc Meis2 in mouse. Then, we depicted the genetic regulatory network (GRNs) of GABAergic neuron subclasses, which showed the conserved and species-specific GRNs for GABAergic neuron cell types. Finally, we investigated the GABAergic neuron subclass-specific expression modules of Alzheimer’s disease (AD)-related genes in GABAergic neuron cell types. Overall, our study reveals the conserved and divergent GABAergic neuron subclasses and GRNs across multiple species and unravels the gene expression modules of AD-risk genes in GABAergic neuron subclasses, facilitating the GABAergic neurons research and clinical treatment. |
| first_indexed | 2024-04-11T16:19:59Z |
| format | Article |
| id | doaj.art-6fa6028f17084d05927de6468ac29aaa |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-11T16:19:59Z |
| publishDate | 2022-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6fa6028f17084d05927de6468ac29aaa2022-12-22T04:14:24ZengNature PortfolioScientific Reports2045-23222022-11-0112111210.1038/s41598-022-21496-7Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s diseaseShiyou Wang0Peiwen Ding1Jingnan Yuan2Haoyu Wang3Xiuqing Zhang4Dongsheng Chen5Dongli Ma6Xingliang Zhang7Fei Wang8College of Life Sciences, University of Chinese Academy of SciencesCollege of Life Sciences, University of Chinese Academy of SciencesCollege of Life Sciences, University of Chinese Academy of SciencesCollege of Life Sciences, University of Chinese Academy of SciencesCollege of Life Sciences, University of Chinese Academy of SciencesBGI-ShenzhenDepartment of Respiratory Diseases, Institute of Pediatrics, Shenzhen Children’s HospitalDepartment of Respiratory Diseases, Institute of Pediatrics, Shenzhen Children’s HospitalBGI-ShenzhenAbstract Understanding the phenotypic and functional diversity of cerebral cortical GABAergic neurons requires a comprehensive analysis of key transcriptional signatures and neuronal subtype identity. However, the diversity and conservation of GABAergic neurons across multiple mammals remain unclear. Here, we collected the single-nucleus RNA sequencing (snRNA-seq) datasets of cerebral cortex from human, macaque, mouse, and pig to identify the conserved neuronal cell types across species. After systematic analysis of the heterogeneity of GABAergic neurons, we defined four major conserved GABAergic neuron subclasses (Inc SST, Inc LAMP5, Inc PVALB, and Inc VIP) across species. We characterized the species-enriched subclasses of GABAergic neurons from four mammals, such as Inc Meis2 in mouse. Then, we depicted the genetic regulatory network (GRNs) of GABAergic neuron subclasses, which showed the conserved and species-specific GRNs for GABAergic neuron cell types. Finally, we investigated the GABAergic neuron subclass-specific expression modules of Alzheimer’s disease (AD)-related genes in GABAergic neuron cell types. Overall, our study reveals the conserved and divergent GABAergic neuron subclasses and GRNs across multiple species and unravels the gene expression modules of AD-risk genes in GABAergic neuron subclasses, facilitating the GABAergic neurons research and clinical treatment.https://doi.org/10.1038/s41598-022-21496-7 |
| spellingShingle | Shiyou Wang Peiwen Ding Jingnan Yuan Haoyu Wang Xiuqing Zhang Dongsheng Chen Dongli Ma Xingliang Zhang Fei Wang Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s disease Scientific Reports |
| title | Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s disease |
| title_full | Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s disease |
| title_fullStr | Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s disease |
| title_full_unstemmed | Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s disease |
| title_short | Integrative cross-species analysis of GABAergic neuron cell types and their functions in Alzheimer’s disease |
| title_sort | integrative cross species analysis of gabaergic neuron cell types and their functions in alzheimer s disease |
| url | https://doi.org/10.1038/s41598-022-21496-7 |
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