Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease
Complex diseases are characterized by spatiotemporal cellular and molecular changes that may be difficult to comprehensively capture. However, understanding the spatiotemporal dynamics underlying pathology can shed light on disease mechanisms and progression. Here we introduce STARmap PLUS, a method...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Science and Business Media LLC
2023
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| Online Access: | https://hdl.handle.net/1721.1/150033 |
| _version_ | 1826198531665297408 |
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| author | Zeng, Hu Huang, Jiahao Zhou, Haowen Meilandt, William J Dejanovic, Borislav Zhou, Yiming Bohlen, Christopher J Lee, Seung-Hye Ren, Jingyi Liu, Albert Tang, Zefang Sheng, Hao Liu, Jia Sheng, Morgan Wang, Xiao |
| author2 | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences |
| author_facet | Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Zeng, Hu Huang, Jiahao Zhou, Haowen Meilandt, William J Dejanovic, Borislav Zhou, Yiming Bohlen, Christopher J Lee, Seung-Hye Ren, Jingyi Liu, Albert Tang, Zefang Sheng, Hao Liu, Jia Sheng, Morgan Wang, Xiao |
| author_sort | Zeng, Hu |
| collection | MIT |
| description | Complex diseases are characterized by spatiotemporal cellular and molecular changes that may be difficult to comprehensively capture. However, understanding the spatiotemporal dynamics underlying pathology can shed light on disease mechanisms and progression. Here we introduce STARmap PLUS, a method that combines high-resolution spatial transcriptomics with protein detection in the same tissue section. As proof of principle, we analyze brain tissues of a mouse model of Alzheimer's disease at 8 and 13 months of age. Our approach provides a comprehensive cellular map of disease progression. It reveals a core-shell structure where disease-associated microglia (DAM) closely contact amyloid-β plaques, whereas disease-associated astrocyte-like (DAA-like) cells and oligodendrocyte precursor cells (OPCs) are enriched in the outer shells surrounding the plaque-DAM complex. Hyperphosphorylated tau emerges mainly in excitatory neurons in the CA1 region and correlates with the local enrichment of oligodendrocyte subtypes. The STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing a tool to pinpoint the molecular and cellular changes underlying pathology. |
| first_indexed | 2024-09-23T11:06:19Z |
| format | Article |
| id | mit-1721.1/150033 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T11:06:19Z |
| publishDate | 2023 |
| publisher | Springer Science and Business Media LLC |
| record_format | dspace |
| spelling | mit-1721.1/1500332023-04-01T03:41:45Z Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease Zeng, Hu Huang, Jiahao Zhou, Haowen Meilandt, William J Dejanovic, Borislav Zhou, Yiming Bohlen, Christopher J Lee, Seung-Hye Ren, Jingyi Liu, Albert Tang, Zefang Sheng, Hao Liu, Jia Sheng, Morgan Wang, Xiao Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences Complex diseases are characterized by spatiotemporal cellular and molecular changes that may be difficult to comprehensively capture. However, understanding the spatiotemporal dynamics underlying pathology can shed light on disease mechanisms and progression. Here we introduce STARmap PLUS, a method that combines high-resolution spatial transcriptomics with protein detection in the same tissue section. As proof of principle, we analyze brain tissues of a mouse model of Alzheimer's disease at 8 and 13 months of age. Our approach provides a comprehensive cellular map of disease progression. It reveals a core-shell structure where disease-associated microglia (DAM) closely contact amyloid-β plaques, whereas disease-associated astrocyte-like (DAA-like) cells and oligodendrocyte precursor cells (OPCs) are enriched in the outer shells surrounding the plaque-DAM complex. Hyperphosphorylated tau emerges mainly in excitatory neurons in the CA1 region and correlates with the local enrichment of oligodendrocyte subtypes. The STARmap PLUS method bridges single-cell gene expression profiles with tissue histopathology at subcellular resolution, providing a tool to pinpoint the molecular and cellular changes underlying pathology. 2023-03-31T13:38:31Z 2023-03-31T13:38:31Z 2023-03 2023-03-31T13:33:21Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/150033 Zeng, Hu, Huang, Jiahao, Zhou, Haowen, Meilandt, William J, Dejanovic, Borislav et al. 2023. "Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease." Nature Neuroscience, 26 (3). en 10.1038/s41593-022-01251-x Nature Neuroscience Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Springer Science and Business Media LLC bioRxiv |
| spellingShingle | Zeng, Hu Huang, Jiahao Zhou, Haowen Meilandt, William J Dejanovic, Borislav Zhou, Yiming Bohlen, Christopher J Lee, Seung-Hye Ren, Jingyi Liu, Albert Tang, Zefang Sheng, Hao Liu, Jia Sheng, Morgan Wang, Xiao Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease |
| title | Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease |
| title_full | Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease |
| title_fullStr | Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease |
| title_full_unstemmed | Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease |
| title_short | Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease |
| title_sort | integrative in situ mapping of single cell transcriptional states and tissue histopathology in a mouse model of alzheimer s disease |
| url | https://hdl.handle.net/1721.1/150033 |
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