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Single nucleus RNA sequencing data of Lewy Body Dementia (LBD) brains

GSE235914 Homo sapiens Expression profiling by high throughput sequencing 8 samples Submitted 2024/09/18 Platform GPL20301
Summary
Aggregated α-synuclein (α-SYN) proteins, encoded by the SNCA gene, are hallmarks of Lewy body disease (LBD), affecting multiple brain regions. However, the specific mechanisms underlying α-SYN pathology in cortical neurons, crucial for LBD-associated dementia, remain unclear. Here, we generated human cortical LBD models by differentiating induced pluripotent stem cells (iPSCs) from SNCA triplication LBD patients into cerebral organoids and observed increased levels of pathological α-SYN in these organoids. Single-cell RNA sequencing revealed prominent expression of the SNCA gene in excitatory neurons, which exhibited synaptic and mitochondrial dysfunction, consistent with findings in the cortex of LBD human brains. Furthermore, screening 1280 FDA-approved drugs identified four candidates, which inhibited α-SYN seeding in RT-QuIC assay, reduced α-SYN aggregation and alleviated mitochondrial dysfunction in SNCA triplication iPSC models. Our findings provide valuable insights into the development of cortical LBD models and the discovery of potential drugs targeting α-SYN aggregation.
Published in
Modeling Lewy body disease with SNCA triplication iPSC-derived cortical organoids and identifying therapeutic drugs
Jin Y, Li F, Li Z et al. · Science advances 2024 · PMID 39259788 · doi:10.1126/sciadv.adk3700
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Direct links to NCBI, no account and no request form: the whole study as GSE235914_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 8 samples. Raw sequencing reads are also available from ENA.

Also filed as BioProject PRJNA988028 and SRA study SRP446189. Searching any of these in the dataset finder brings you back here.

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