GEO series

Intersecting impact of CAG repeat and Huntingtin knockout in stem cell-derived cortical neurons

GSE284565 Homo sapiens (human) RNA-seq (gene expression) 15 samples Submitted 2025/04/29 Platform GPL24676

At a glance

RNA-seq (gene expression) · human · 15 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: Homo sapiens (human)
Samples: 15 samples: 5 conditions, mostly in triplicateGroups 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: Intersecting impact of CAG repeat and huntingtin knockout in stem cell-derived cortical neuronsNeurobiology of disease · 2025

Summary (written by the submitters)

Huntington’s Disease (HD) is caused by a CAG repeat expansion in the gene encoding Huntingtin (HTT). While normal HTT function appears impacted by the mutation, the specific pathways unique to CAG repeat expansion versus loss of normal function are unclear.

Read the full summary ↓

To understand the impact of the CAG repeat expansion, we evaluated biological signatures of HTT knockout (HTT KO) versus those that occur from the CAG repeat expansion by applying multi-omics, live cell imaging, survival analysis and a novel feature- based pipeline to study cortical neurons (eCNs) derived from an isogenic human embryonic stem cell series (RUES2). HTT KO and the CAG repeat expansion influence developmental trajectories of eCNs, with opposing effects on the growth. Network analyses of differentially expressed genes and proteins associated with enriched epigenetic motifs identified subnetworks common to CAG repeat expansion and HTT KO that include neuronal differentiation, cell cycle regulation, and mechanisms related to transcriptional repression and may represent gain-of-function mechanisms that cannot be explained by HTT loss of function alone. A combination of dominant and loss-of-function mechanisms are likely involved in the aberrant neurodevelopmental and neurodegenerative features of HD that can help inform therapeutic strategies.

Published in

Intersecting impact of CAG repeat and huntingtin knockout in stem cell-derived cortical neurons

Stocksdale JT, Leventhal MJ, Lam S et al. · Neurobiology of disease 2025 · PMID 40258535 · doi:10.1016/j.nbd.2025.106914

This dataset

Open GSE284565 in finder → Find more human 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 GSE284565_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 PRJNA1199548 and SRA study SRP552105. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40258535) ↗

Study design

5 conditions, mostly in triplicate

20CAGn1 RUES2 cells (parental line), ×3 20CAGn2 RUES2 cells, ×3 72CAGn1 RUES2 cells ×3 HTT KO RUES2 cells, ×3 56CAG RUES2 cells, ×2 56CAG RUES2 cells ×1

Supports a between-group comparison across 14 samples.

How we read this: 5 replicated groups read from 15 sample titles; they account for 14 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

GSM8686907 20CAGn1 RUES2 cells (parental line), replicate 1 20CAGn1 RUES2 cells (pa…
GSM8686908 20CAGn2 RUES2 cells, replicate 1 20CAGn2 RUES2 cells,
GSM8686909 56CAG RUES2 cells, replicate 1 56CAG RUES2 cells,
GSM8686910 72CAGn1 RUES2 cells replicate 1 72CAGn1 RUES2 cells
GSM8686911 HTT KO RUES2 cells, replicate 1 HTT KO RUES2 cells,
GSM8686912 20CAGn1 RUES2 cells (parental line), replicate 2 20CAGn1 RUES2 cells (pa…
GSM8686913 20CAGn2 RUES2 cells, replicate 2 20CAGn2 RUES2 cells,
GSM8686914 56CAG RUES2 cells replicate 2
GSM8686915 72CAGn1 RUES2 cells replicate 2 72CAGn1 RUES2 cells
GSM8686916 HTT KO RUES2 cells, replicate 2 HTT KO RUES2 cells,
GSM8686917 20CAGn1 RUES2 cells (parental line), replicate 3 20CAGn1 RUES2 cells (pa…
GSM8686918 20CAGn2 RUES2 cells, replicate 3 20CAGn2 RUES2 cells,
GSM8686919 56CAG RUES2 cells, replicate 3 56CAG RUES2 cells,
GSM8686920 72CAGn1 RUES2 cells replicate 3 72CAGn1 RUES2 cells
GSM8686921 HTT KO RUES2 cells, replicate 3 HTT KO RUES2 cells,

Datasets on a similar topic

GSE284798 Intersecting impact of CAG repeat and Huntingtin knockout in stem cell-derived cortical neurons [cortical_bulkRNASeq] 16 samples shares cag, intersecting, cell-derived, huntingtin, knockout, cortical, neurons, impact
GSE282628 Intersecting impact of CAG repeat and Huntingtin knockout in stem cell-derived cortical neurons [ESC] 75 samples shares cag, intersecting, cell-derived, huntingtin, knockout, cortical, neurons, impact
GSE282626 Intersecting impact of CAG repeat and Huntingtin knockout in stem cell-derived cortical neurons [cortical] 75 samples shares cag, intersecting, cell-derived, huntingtin, knockout, cortical, neurons, impact
GSE264218 Sequencing-Guided Design of Genetically Encoded Small RNAs Targeting CAG Repeats for Selective Inhibition of Mutant Huntingtin [II] 18 samples shares cag, huntingtin
GSE264444 Sequencing-Guided Design of Genetically Encoded Small RNAs Targeting CAG Repeats for Selective Inhibition of Mutant Huntingtin 41 samples shares cag, huntingtin
GSE275240 ACE2 knockout hinders SARS-CoV-2 propagation in iPS cell-derived airway and alveolar epithelial cells 18 samples shares cell-derived, knockout
GSE326651 in vivo human embryonic spinal cord atlas validates stem cell-derived human dorsal interneurons and reveals ASD spinal signatures [day0NMP_bulk RNAseq] 15 samples shares cell-derived, neurons
GSE326655 in vivo human embryonic spinal cord atlas validates stem cell-derived human dorsal interneurons and reveals ASD spinal signatures [day43NMP_scRNAseq] 12 samples shares cell-derived, neurons

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