GEO series

Mapping the ISR Landscape in Cognitive Disorders via single-cell multi-omics

GSE314068 Mus musculus (mouse) Single-cell RNA-seq 28 samples Submitted 2026/07/01 Platform GPL34328

At a glance

Single-cell RNA-seq · mouse · 28 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism: Mus musculus (mouse)
Samples: 28 samples: 28 samples, each with a distinct title — no replicated groupsGroups are read from the sample names, not from the paper. Check the list below.
Data you can get: A processed table (series matrix) and supplementary files from NCBI; the raw sequencing reads from ENA. Which of these hold counts depends on the study, so check the file list.

Summary (written by the submitters)

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.

Read the full summary ↓

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

Open GSE314068 in finder → Find more mouse RNA-seq datasets →

Download · which file do I need?

Direct links to NCBI and ENA, no account and no request form. Pick by what you want to do: take the small processed table to look, the supplementary files to re-analyse, or the original raw data to start over.

1 · Just have a look

Processed table

The series matrix: one table of values per sample as the submitters processed it. The smallest download, and it opens in Excel or R. Start here to see what the data look like.

Series matrix ↓

2 · Re-analyse it

Supplementary files

The count tables and other files the authors uploaded. Take only the samples you need, or the whole study as GSE314068_RAW.tar (it can run to tens of gigabytes).

All supplementary files ↗ Whole study · RAW.tar ↓

3 · Start from the raw reads

Raw sequencing reads

The original FASTQ files, straight from the sequencer, held at ENA. Large, and you align them yourself, so only choose this if you need to re-process the study from scratch.

Raw reads on ENA ↗

What the files usually look like: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1389920 and SRA study SRP655940. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

28 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 28 sample titles: 28 distinct titles with little repetition. These groups are guessed from the sample names, not taken from the paper, so check them against the sample list below before relying on them.

Samples in this study

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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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.