GEO series
Mapping the ISR Landscape in Cognitive Disorders via single-cell multi-omics
GSE314068
Mus musculus
Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing
28 samples
Submitted 2026/07/01
Platform GPL34328
Summary
Persistent activation of the integrated stress response (ISR) is a central driver of cognitive decline in both neurodevelopmental and neurodegenerative disorders. However, the cell-type-specific mechanisms underlying these deficits remain poorly understood. Here, by integrating single-cell RNA-seq and single-cell ATAC-seq, we generated an ISR atlas of the brain using Ppp1r15bR658C mice, a clinically relevant model of intellectual disability characterized by selective and persistent ISR activation. Unexpectedly, our analysis revealed that distinct brain cell types differentially engage transcriptional and chromatin remodeling programs. Notably, selective deletion of the major ISR downstream effector ATF4 in GABAergic neurons—but not in glutamatergic neurons—impacts ISR-mediated cognitive decline in Ppp1r15bR658C mice, demonstrating that different neuronal subtypes have different dependencies for ISR effectors. Finally, we defined a molecular single-cell signature of persistent ISR activation that serves as a metric of ISR-mediated cellular vulnerability, and as a biomarker for cognitive dysfunction across human cogntive disorders. These findings dissect the cell-type-specific architecture of the ISR in the brain, providing new insights into the biological mechanisms driving ISR-dependent cognitive decline.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE314068_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 28 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1389920 and SRA study SRP655940. Searching any of these in the dataset finder brings you back here.
Study design
28 conditions, each sampled once — no replicated groups
Read from 28 sample titles: 28 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
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- GSM9381026 Cortical nuclei, Ppp1r15b-R658C, Female, Rep A2, Gene Expression
- GSM9381027 Cortical nuclei, Ppp1r15b-R658C, Female, Rep A2, ATAC-seq
- GSM9381028 Cortical nuclei, Ppp1r15b-R658C, Male, Rep A3, Gene Expression
- GSM9381029 Cortical nuclei, Ppp1r15b-R658C, Male, Rep A3, ATAC-seq
- GSM9381030 Cortical nuclei, Ppp1r15b-R658C, Male, Rep A10, Gene Expression
- GSM9381031 Cortical nuclei, Ppp1r15b-R658C, Male, Rep A10, ATAC-seq
- GSM9381032 Cortical nuclei, Wild Type, Female, Rep B11, Gene Expression
- GSM9381033 Cortical nuclei, Wild Type, Female, Rep B11, ATAC-seq
- GSM9381034 Cortical nuclei, Wild Type, Female, Rep F1, Gene Expression
- GSM9381035 Cortical nuclei, Wild Type, Female, Rep F1, ATAC-seq
- GSM9381036 Cortical nuclei, Wild Type, Male, Rep M3, Gene Expression
- GSM9381037 Cortical nuclei, Wild Type, Male, Rep M3, ATAC-seq
- GSM9381038 Cortical nuclei, Ppp1r15b-R658C, Male, Rep A0, Gene Expression
- GSM9381039 Cortical nuclei, Ppp1r15b-R658C, Male, Rep A0, ATAC-seq
- GSM9381040 Cortical nuclei, Ppp1r15b-R658C, Female, Rep A10, Gene Expression
- GSM9381041 Cortical nuclei, Ppp1r15b-R658C, Female, Rep A10, ATAC-seq
- GSM9381042 Cortical nuclei, Ppp1r15b-R658C, Male, Rep B0, Gene Expression
- GSM9381043 Cortical nuclei, Ppp1r15b-R658C, Male, Rep B0, ATAC-seq
- GSM9381044 Cortical nuclei, Ppp1r15b-R658C, Female, Rep B10, Gene Expression
- GSM9381045 Cortical nuclei, Ppp1r15b-R658C, Female, Rep B10, ATAC-seq
- GSM9381046 Cortical nuclei, Wild Type, Female, Rep B20, Gene Expression
- GSM9381047 Cortical nuclei, Wild Type, Female, Rep B20, ATAC-seq
- GSM9381048 Cortical nuclei, Wild Type, Female, Rep F2, Gene Expression
- GSM9381049 Cortical nuclei, Wild Type, Female, Rep F2, ATAC-seq
- GSM9381050 Cortical nuclei, Wild Type, Male, Rep M1, Gene Expression
- GSM9381051 Cortical nuclei, Wild Type, Male, Rep M1, ATAC-seq
- GSM9381052 Cortical nuclei, Wild Type, Male, Rep M2, Gene Expression
- GSM9381053 Cortical nuclei, Wild Type, Male, Rep M2, ATAC-seq
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