GSE140670 AD-linked TREM2 Mutation Induces Unique Transcriptional Cell States Associated with Toxic Function in Tauopathy

Contributors : Faten A Sayed ; Lay Kodama ; Joe C Udeochu ; Hansruedi Mathys ; David Le ; Xiang Niu ; Linas Mazutis ; Lu Zhou ; Xueqiao Jiang ; Tara E Tracy ; Xueting Wang ; Fuying Gao ; Maria Telpoukhovskaia ; Gillian K Carling ; Yueming Li ; Georgia Frost ; Yungui Zhou ; Yaqiao Li ; Zuolin Cheng ; Guoqian Yu ; Qingyun Li ; John Hardy ; Giovanni Coppola ; Li-Huei Tsai ; Li GanSeries Type : Expression profiling by high throughput sequencingOrganism : Mus musculusThe hemizygous R47H variant of TREM2, a microglia-specific gene in the brain, increases risk for late-onset Alzheimer ’s disease (AD). To understand its pathogenicity, we generated knock-in mice in which mouse Trem2 was replaced with wild-type or R47H human TREM2. One allele of R47H-hTREM2 was sufficient to induce cognitive deficits and alter synaptic transmission. In knock-in mice with tau inclusions, R47HhTREM 2 exacerbated spatial learning and memory deficits only in female mice. Bulk and single-nuclei RNA-sequencing of hippocampal tissue from female tauopathy mice revealed R47H-induced upregulation of cytokine signaling and microglial clusters with unique R47H-associated signatures. Single-nuclei RNA-s equencing of cortex from AD patients with and without R47H-TREM2 established transcriptomic changes in glial populations that correlated significantly with those observed in the R47H tauopathy mouse model. By unraveling disease-enhancing properties of the R47H mutation, our findings provid...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Mus musculus Source Type: research