Integrative in situ mapping of single-cell transcriptional states and tissue histopathology in a mouse model of Alzheimer’s disease
Name
2022.01.14.476072v1.full.pdf
Description
Submitted version
Size
22.97 MB
Format
Adobe PDF
Checksum (MD5)
c4c37a4fa35dc7d209cbba354ed69ec3
Author(s)
Zeng, Hu
Huang, Jiahao
Zhou, Haowen
Meilandt, William J
Dejanovic, Borislav
Zhou, Yiming
Bohlen, Christopher J
Lee, Seung-Hye
Ren, Jingyi
Liu, Albert
Date Issued
March 2023
Journal
Nature Neuroscience
Publisher
Springer Science and Business Media LLC
Citation
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).
Version
Original manuscript
Abstract
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.
MIT Department
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
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Creative Commons Attribution-Noncommercial-Share Alike
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DOI of Published Version
https://doi.org/10.1038/s41593-022-01251-x
