Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease
Abstract Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer’s disease (AD), but little is known about the molecular mechanisms underlying this regional vulnerability. Here we utilize the 10 × Visium platform to define the spatial transcriptomic profile in both AD and c...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-12-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-022-01494-6 |
| _version_ | 1797977179141701632 |
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| author | Shuo Chen Yuzhou Chang Liangping Li Diana Acosta Yang Li Qi Guo Cankun Wang Emir Turkes Cody Morrison Dominic Julian Mark E. Hester Douglas W. Scharre Chintda Santiskulvong Sarah XueYing Song Jasmine T. Plummer Geidy E. Serrano Thomas G. Beach Karen E. Duff Qin Ma Hongjun Fu |
| author_facet | Shuo Chen Yuzhou Chang Liangping Li Diana Acosta Yang Li Qi Guo Cankun Wang Emir Turkes Cody Morrison Dominic Julian Mark E. Hester Douglas W. Scharre Chintda Santiskulvong Sarah XueYing Song Jasmine T. Plummer Geidy E. Serrano Thomas G. Beach Karen E. Duff Qin Ma Hongjun Fu |
| author_sort | Shuo Chen |
| collection | DOAJ |
| description | Abstract Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer’s disease (AD), but little is known about the molecular mechanisms underlying this regional vulnerability. Here we utilize the 10 × Visium platform to define the spatial transcriptomic profile in both AD and control (CT) MTG. We identify unique marker genes for cortical layers and the white matter, and layer-specific differentially expressed genes (DEGs) in human AD compared to CT. Deconvolution of the Visium spots showcases the significant difference in particular cell types among cortical layers and the white matter. Gene co-expression analyses reveal eight gene modules, four of which have significantly altered co-expression patterns in the presence of AD pathology. The co-expression patterns of hub genes and enriched pathways in the presence of AD pathology indicate an important role of cell–cell-communications among microglia, oligodendrocytes, astrocytes, and neurons, which may contribute to the cellular and regional vulnerability in early AD. Using single-molecule fluorescent in situ hybridization, we validated the cell-type-specific expression of three novel DEGs (e.g., KIF5A, PAQR6, and SLC1A3) and eleven previously reported DEGs associated with AD pathology (i.e., amyloid beta plaques and intraneuronal neurofibrillary tangles or neuropil threads) at the single cell level. Our results may contribute to the understanding of the complex architecture and neuronal and glial response to AD pathology of this vulnerable brain region. |
| first_indexed | 2024-04-11T05:02:49Z |
| format | Article |
| id | doaj.art-2440d9d04a75482092b0985a2c1cb523 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-04-11T05:02:49Z |
| publishDate | 2022-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-2440d9d04a75482092b0985a2c1cb5232022-12-25T12:33:42ZengBMCActa Neuropathologica Communications2051-59602022-12-0110112410.1186/s40478-022-01494-6Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s diseaseShuo Chen0Yuzhou Chang1Liangping Li2Diana Acosta3Yang Li4Qi Guo5Cankun Wang6Emir Turkes7Cody Morrison8Dominic Julian9Mark E. Hester10Douglas W. Scharre11Chintda Santiskulvong12Sarah XueYing Song13Jasmine T. Plummer14Geidy E. Serrano15Thomas G. Beach16Karen E. Duff17Qin Ma18Hongjun Fu19Department of Neuroscience, College of Medicine, Ohio State UniversityBiomedical Sciences Graduate Program, Ohio State UniversityDepartment of Neuroscience, College of Medicine, Ohio State UniversityDepartment of Neuroscience, College of Medicine, Ohio State UniversityDepartment of Biomedical Informatics, College of Medicine, Ohio State UniversityBiomedical Sciences Graduate Program, Ohio State UniversityDepartment of Biomedical Informatics, College of Medicine, Ohio State UniversityUK Dementia Research Institute, UCL Queen Square Institute of NeurologyDepartment of Neuroscience, College of Medicine, Ohio State UniversityThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children’s HospitalThe Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute at Nationwide Children’s HospitalDepartment of Neurology, Center for Cognitive and Memory Disorders, Center for Neuromodulation, Ohio State UniversityDepartment of Biomedical Sciences, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Cedars-Sinai Medical CenterDepartment of Biomedical Sciences, Cedars-Sinai Medical CenterBanner Sun Health Research InstituteBanner Sun Health Research InstituteUK Dementia Research Institute, UCL Queen Square Institute of NeurologyDepartment of Biomedical Informatics, College of Medicine, Ohio State UniversityDepartment of Neuroscience, College of Medicine, Ohio State UniversityAbstract Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer’s disease (AD), but little is known about the molecular mechanisms underlying this regional vulnerability. Here we utilize the 10 × Visium platform to define the spatial transcriptomic profile in both AD and control (CT) MTG. We identify unique marker genes for cortical layers and the white matter, and layer-specific differentially expressed genes (DEGs) in human AD compared to CT. Deconvolution of the Visium spots showcases the significant difference in particular cell types among cortical layers and the white matter. Gene co-expression analyses reveal eight gene modules, four of which have significantly altered co-expression patterns in the presence of AD pathology. The co-expression patterns of hub genes and enriched pathways in the presence of AD pathology indicate an important role of cell–cell-communications among microglia, oligodendrocytes, astrocytes, and neurons, which may contribute to the cellular and regional vulnerability in early AD. Using single-molecule fluorescent in situ hybridization, we validated the cell-type-specific expression of three novel DEGs (e.g., KIF5A, PAQR6, and SLC1A3) and eleven previously reported DEGs associated with AD pathology (i.e., amyloid beta plaques and intraneuronal neurofibrillary tangles or neuropil threads) at the single cell level. Our results may contribute to the understanding of the complex architecture and neuronal and glial response to AD pathology of this vulnerable brain region.https://doi.org/10.1186/s40478-022-01494-6Spatially resolved transcriptomicsAlzheimer’s diseaseVulnerabilityHuman middle temporal gyrusMicrogliaOligodendrocytes |
| spellingShingle | Shuo Chen Yuzhou Chang Liangping Li Diana Acosta Yang Li Qi Guo Cankun Wang Emir Turkes Cody Morrison Dominic Julian Mark E. Hester Douglas W. Scharre Chintda Santiskulvong Sarah XueYing Song Jasmine T. Plummer Geidy E. Serrano Thomas G. Beach Karen E. Duff Qin Ma Hongjun Fu Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease Acta Neuropathologica Communications Spatially resolved transcriptomics Alzheimer’s disease Vulnerability Human middle temporal gyrus Microglia Oligodendrocytes |
| title | Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease |
| title_full | Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease |
| title_fullStr | Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease |
| title_full_unstemmed | Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease |
| title_short | Spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in Alzheimer’s disease |
| title_sort | spatially resolved transcriptomics reveals genes associated with the vulnerability of middle temporal gyrus in alzheimer s disease |
| topic | Spatially resolved transcriptomics Alzheimer’s disease Vulnerability Human middle temporal gyrus Microglia Oligodendrocytes |
| url | https://doi.org/10.1186/s40478-022-01494-6 |
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