GEO series

Stem cell-derived human glutamatergic neurons with pathogenic KCNQ2 variants display hyperactive bursting phenotypes

GSE291694 Mus musculus (mouse) RNA-seq (gene expression) 42 samples Submitted 2026/01/12 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 42 samples

What it is: RNA-seq (gene expression)Gene activity measured by sequencing. The summary does not mention single-cell work, so this is most likely bulk: one average per sample, the usual starting point for comparing groups.
Organism: Mus musculus (mouse)
Samples: 42 samples: 6 conditions, mostly with about 7 replicates eachGroups 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.
Paper: Human iPSC-derived glutamatergic neurons with pathogenic KCNQ2 variants display hyperactive bursting phenotypesNeurobiology of disease · 2025

Summary (written by the submitters)

Pathogenic variants in the KCNQ2 gene, which encodes a potassium channel subunit, are associated with neonatal seizures, epileptic encephalopathy, intellectual disability, and autism. Although the consequences of disrupted KCNQ2 channel function have been studied in the past, the detailed molecular mechanisms underlying the development of neurological phenotypes remain unclear, and neuronal models of specific patient variants are lacking.

Read the full summary ↓

We generated patient-specific induced pluripotent stem cells (iPSCs) from fibroblasts from three individuals with distinct KCNQ2 pathogenic variants. We corrected the KCNQ2 variants using CRISPR-Cas9 editing to create isogenic controls and differentiated these iPSCs into glutamatergic neurons to study the effects of each variant on neuronal function. The three KCNQ2 variants were: 1) KCNQ2 c.875_877delTCCinsCCT, L292_L293delinsPF, 2) KCNQ2 c.766G>T, G256W, and 3) KCNQ2 c.821C>T, T274M. Our data revealed longer neurite outgrowth in two patient lines (T274M and G256W). Transcriptional profiling showed that all three KCNQ2 lines had increased expression of genes involved in synaptic transmission/signaling, cell adhesion, and GTPase signal transduction. Functional analyses of neuronal networks revealed increased burst duration in all three KCNQ2 lines compared with their isogenic controls. Furthermore, neurons from the L292_L293delinsPF and T274M lines displayed increased network connectivity associated with increased density of synaptic markers. Finally, we detected hyperexcitable neuronal networks in the G256W line with electrical stimulation of the neural networks on a high-density microelectrode array, and this phenotype was rescued with retigabine. These disease-related phenotypes for each of the KCNQ2 pathogenic variants can be used for drug screening to identify treatment options for the patients.

Published in

Human iPSC-derived glutamatergic neurons with pathogenic KCNQ2 variants display hyperactive bursting phenotypes

Sundberg M, Shum C, Norabuena EM et al. · Neurobiology of disease 2025 · PMID 41015095 · doi:10.1016/j.nbd.2025.107126

This dataset

Open GSE291694 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 GSE291694_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: For RNA-seq the counts are usually a table among the supplementary files (look for 'counts', 'expression', 'FPKM' or 'TPM' in the file name). The series matrix of a sequencing study is sometimes nearly empty.

Also filed as BioProject PRJNA1234669 and SRA study SRP569697. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41015095) ↗

Study design

6 conditions, mostly with about 7 replicates each

isoL292_293 ×7 L292_293/+ ×7 isoT274M ×7 T274M/+ ×7 isoG256W ×7 G256W/+ ×7

Supports a between-group comparison across 42 samples.

How we read this: 6 replicated groups read from 42 sample titles; they account for 42 of them. 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

GSM8840098 isoL292_293-1 isoL292_293
GSM8840099 isoL292_293-2 isoL292_293
GSM8840100 isoL292_293-3 isoL292_293
GSM8840101 L292_293/+-1 L292_293/+
GSM8840102 L292_293/+-2 L292_293/+
GSM8840103 L292_293/+-3 L292_293/+
GSM8840104 isoT274M-1 isoT274M
GSM8840105 isoT274M-2 isoT274M
GSM8840106 isoT274M-3 isoT274M
GSM8840107 T274M/+-1 T274M/+
GSM8840108 T274M/+-2 T274M/+
GSM8840109 T274M/+-3 T274M/+
GSM8840110 isoG256W-1 isoG256W
GSM8840111 isoG256W-2 isoG256W
GSM8840112 isoG256W-3 isoG256W
GSM8840113 G256W/+-1 G256W/+
GSM8840114 G256W/+-2 G256W/+
GSM8840115 G256W/+-3 G256W/+
GSM8840116 isoG256W-4 isoG256W
GSM8840117 isoG256W-5 isoG256W
GSM8840118 isoG256W-6 isoG256W
GSM8840119 isoG256W-7 isoG256W
GSM8840120 isoT274M-4 isoT274M
GSM8840121 isoT274M-5 isoT274M
GSM8840122 isoT274M-6 isoT274M
GSM8840123 isoT274M-7 isoT274M
GSM8840124 isoL292_293-4 isoL292_293
GSM8840125 isoL292_293-5 isoL292_293
GSM8840126 isoL292_293-6 isoL292_293
GSM8840127 isoL292_293-7 isoL292_293
GSM8840128 L292_293/+-4 L292_293/+
GSM8840129 L292_293/+-5 L292_293/+
GSM8840130 L292_293/+-6 L292_293/+
GSM8840131 L292_293/+-7 L292_293/+
GSM8840132 G256W/+-4 G256W/+
GSM8840133 G256W/+-5 G256W/+
GSM8840134 G256W/+-6 G256W/+
GSM8840135 G256W/+-7 G256W/+
GSM8840136 T274M/+-4 T274M/+
GSM8840137 T274M/+-5 T274M/+

+ 2 more — browse all 42 samples with per-sample file links →

Datasets on a similar topic

GSE297403 γδ+ T cell-derived IL-17A stimulates airway epithelial/stromal cells to secrete G-CSF, promoting lung-specific pathogenic Siglec-F+ neutrophil development in PPE-induced emphysema 6 samples shares cell-derived, pathogenic
GSE267419 Retinal ganglion cell-derived semaphorin 6A segregates starburst amacrine cell dendritic scaffolds to organize the mouse inner retina 855 samples shares cell-derived
GSE271004 Transcriptional Analyses of Acinar- And Ductal-Cell-Derived Pancreatic Cancer 59 samples shares cell-derived
GSE218858 Hyperactive STAT5 Hijacks T-Cell Receptor Signaling and Drives Immature T-Cell Acute Lymphoblastic Leukemia 51 samples shares hyperactive
GSE309633 Sex-Dependent Effects of Glutamatergic Disruption on Dopaminergic Neuron Subtype Vulnerable in Parkinson’s Disease 48 samples shares glutamatergic
GSE277881 Hyperactive PI3K-delta in Th1 and Th2 differentiation [RNA-seq] 42 samples shares hyperactive
GSE291068 Trophectoderm-like cells from EPS cells enable generating EPS cell-derived post-implantation embryoids that complete gastrulation [bulk RNA-seq] 34 samples shares cell-derived
GSE279403 Dietary cysteine enhances intestinal stemness via CD8+ T cell-derived IL-22 28 samples shares cell-derived

Search all mouse RNA-seq datasets in GEO →

Share this dataset

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.