Spatial Transcriptomics and In Situ Sequencing to Study Alzheimer's Disease.
By Wei-Ting Chen, Ashley Lu, K. Craessaerts, B. Pavie, Carlo Sala Frigerio, N. Corthout, Xiao-hang Qian, J. Laláková, M. Kühnemund, I. Voytyuk and 13 more. Cell, 2020
766 citations recorded by the source corpus.
Although complex inflammatory-like alterations are observed around the amyloid plaques of Alzheimer's disease (AD), little is known about the molecular changes and cellular interactions that characterize this response. We investigate here, in an AD mouse model, the transcriptional changes occurring in tissue domains in a 100-μm diameter around amyloid plaques using spatial transcriptomics. We demonstrate early alterations in a gene co-expression network enriched for myelin and oligodendrocyte genes (OLIGs), whereas a multicellular gene co-expression network of plaque-induced genes (PIGs) involving the complement system, oxidative stress, lysosomes, and inflammation is prominent in the later phase of the disease. We confirm the majority of the observed alterations at the cellular level using in situ sequencing on mouse and human brain sections. Genome-wide spatial transcriptomics analysis provides an unprecedented approach to untangle the dysregulated cellular network in the vicinity of pathogenic hallmarks of AD and other brain diseases.
Subfields: Immunology, Molecular Biology, Neurology
View Paper: https://www.semanticscholar.org/paper/68c9f35b659c74b8dd091dd85e9371c50e5410c4
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In Molecular Biology
Citations in the corpus
- Spatial components of molecular tissue biology (2022, neutral): “Several recent studies follow this approach in conditions as diverse as cancer 34,35,85–89 , myocardial infarction 90 and neurodegenerative diseases 91 .”
- An introduction to spatial transcriptomics for biomedical research (2022, background): “One study employed Spatial Transcriptomics to determine gene modules expressed in the local vicinity of amyloid plaques in murine Alzheimer’s disease model [31].”
- Spatially informed clustering, integration, and deconvolution of spatial transcriptomics with GraphST (2023, neutral): “Of the DCIS/LCIS regions, 4 and 5 only had macrophage/DC/monocytes present, while 1 and 2 had no immune cells mapped onto them.”