← BioTransfer GEO Dataset Finder
GEO series

Modulating alternative splicing of MECP2: A potential therapeutic strategy for Rett syndrome

GSE268177 Homo sapiens (human) RNA-seq (gene expression) 93 samples Submitted 2026/04/15 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 93 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
93 samples: 21 conditions, mostly with about 4 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
Modulating alternative splicing of MECP2 is a potential therapeutic strategy for Rett syndromeScience translational medicine · 2026
Summary (written by the submitters)
Rett syndrome (RTT) is a neurological disorder caused by loss-of-function mutations in methyl CpG binding protein 2 (MECP2), a transcriptional regulator essential for maintenance of normal neuronal function. The current FDA-approved treatment for RTT, Trofinetide, mildly alleviates some symptoms. In contrast, re-introducing MeCP2 or upregulating it through transgenesis in mouse RTT models improves most neurological phenotypes and enhances survival.
Read the full summary ↓
Here, we devised a therapeutic strategy to moderately increase MeCP2 protein by modulating the alternative splicing of MECP2 to switch the less efficiently translated e2 to the more efficiently translated e1 isoform. We deleted Mecp2 exon 2 (unique to e2), leading to production of only e1 mRNA, and show this upregulates MeCP2 by 50-60% in mice. Next, using two independent RTT induced pluripotent stem cell (iPSC)-derived neuron models harboring mutations that reduce both MeCP2 expression and function, we show that exon 2 deletion upregulates MeCP2 and ameliorates morphological and electrophysiological deficits in these neurons. Isoform switching also significantly corrects the dysregulated transcriptome in RTT neurons. Lastly, an exon 2-skipping Morpholino upregulates MeCP2-E1 in vivo. These data set the stage for a promising therapeutic strategy using antisense oligonucleotides to promote isoform switching in patients with RTT who carry partially functioning alleles of MECP2.
Published in
Modulating alternative splicing of MECP2 is a potential therapeutic strategy for Rett syndrome
Tirumala HP, Wang L, Li Y et al. · Science translational medicine 2026 · PMID 41779872 · doi:10.1126/scitranslmed.adq4529
This dataset
Open GSE268177 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 GSE268177_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 PRJNA1115045 and SRA study SRP509369. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41779872) ↗
Study design
21 conditions, mostly with about 4 replicates each
Isogenic Control (WT); Clone#32; technical ×6 G118E; Clone#15; technical ×6 G118E-E2KO; Clone#21; technical ×6 Isogenic Control (WT); Clone#42; technical ×6 G118E; Clone#20; technical ×6 G118E-E2KO; Clone#25; technical ×6 G118E;Clone#15;1month; technical ×4 Isogenic WT Control; Clone#32;1month; technic… ×4 +13 more

Supports a between-group comparison across 93 samples.

How we read this: 21 replicated groups read from 93 sample titles; they account for 93 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

+ 53 more — browse all 93 samples with per-sample file links →

Datasets on a similar topic

Search all human 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.