Comparative analysis of transcriptome remodeling in plaque associated and plaque distant microglia during amyloid-ß pathology progression
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE205048 | GEO | 2022/09/28
REPOSITORIES: GEO
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Project description:In this study, we characterize the transcriptomic alterations, cellular compositions, and signaling perturbations in the amyloid plaque niche in an AD mouse model using high-resolution spatial transcriptomics (CosMx and Stereo-seq). We discover a wide heterogeneity in the cellular composition of amyloid plaque niches, marked by an increase in microglial accumulation over time. We profile the alterations of glial cells as they are exposed to plaques, and conclude that the microglial response to plaques is consistent across different brain regions, while the astrocytic response is more heterogeneous. In turn, as the microglial density of plaque niches increases, astrocytes acquire a more neurotoxic phenotype and play a key role in inducing GABAergic signaling and decreasing glutamatergic signaling in neurons of the hippocampus. Taken together, we show that astrocytic signaling around plaque pathology is disrupted with increasing microglial density, which in turn induces an imbalance in synaptic signaling in neurons in the hippocampus.
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