GEO series

Brain Mecp2 Genetic Dosage and Gene Therapy Shape Multi-omics Signatures and Biomarkers in Rett Syndrome [1]

GSE300534 Mus musculus (mouse) RNA-seq (gene expression) 137 samples Submitted 2026/06/01 Platform GPL34328

At a glance

RNA-seq (gene expression) · mouse · 137 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: 137 samples: 15 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.

Summary (written by the submitters)

Rett syndrome is a neurodevelopmental disorder, caused by mutations in the MECP2 gene. Like other genetic disorders of neurodevelopment, it lacks molecular biomarkers to assess disease and therapy outcomes. We present a strategy to identify mechanisms of disease and biomarkers, which is reliant on a library of brain proteins defined by their responsiveness to Mecp2 gene dosage, and correlated with molecular, and clinical outcomes after AAV9-mediated MECP2 gene therapy into Mecp2-KO mouse brain.

Read the full summary ↓

Gene rescue restored MECP2 brain expression, corrected clinical phenotypes in Mecp2-KO mice, and reverted transcriptome and proteome phenotypes. We identified 327 shared proteins among a total of 1852 proteins in cortex and hippocampus responsive to Mecp2/MECP2. Of these shared proteins, 119 have congruently expressed transcripts. Both the Mecp2-responsive proteome or the congruent 119 transcript-proteins pairs were enriched in synaptic and metabolic pathways including mitochondria carbon and NAD+ metabolism. We used this genetically validated and therapy-responsive library of proteins to inform the selection of putative biomarkers in cerebrospinal fluid of Rett patients. We analyzed cerebrospinal fluid composition of neurotypical and Rett subjects using an ultrasensitive nucleic acid based multiplexed ELISA. We identified 28 proteins altered in Rett patients, 9 of which overlapped with proteins sensitive to gene therapy and dosage. Multivariate regression linked several candidate biomarkers to Mecp2/MECP2 protein abundance and phenotypic improvements in mice. Our paradigm provides a rigorous molecular systems-level framework integrating genetics, preclinical MECP2 gene therapy, and rodent clinical metrics to define robust, cross-species biomarkers and mechanisms in Rett syndrome and other neurodevelopmental disorders.

This dataset

Open GSE300534 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 GSE300534_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 PRJNA1281124 and SRA study SRP593981. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

15 conditions, mostly with about 7 replicates each

Cortex of Mecp2-WT, injected with PBS, contro… ×21 Hippocampus of Mecp2-WT, injected with PBS, c… ×20 Cortex of Mecp2-KO, injected with AAV9-rrt271… ×13 Cortex of Mecp2-KO, injected with AAV9-rrt271… ×12 Hippocampus of Mecp2-KO, injected with AAV9-r… ×12 Hippocampus of Mecp2-KO, injected with AAV9-r… ×11 Hippocampus of Tau+/+, Control for Tau driven… ×8 Cortex of Tau-/+, Tau driven overexpression o… ×7 +9 more

Supports a case/control comparison: 14 samples read as cases, 58 as controls.

How we read this: 15 replicated groups read from 137 sample titles; they account for 135 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

GSM9063950 Cortex of Mecp2-KO, non-injected control, biol rep 1 Cortex of Mecp2-KO, non…
GSM9063951 Cortex of Mecp2-KO, non-injected control, biol rep 2 Cortex of Mecp2-KO, non…
GSM9063952 Cortex of Mecp2-WT, injected with PBS, control, biol rep 1 Cortex of Mecp2-WT, inj…
GSM9063953 Cortex of Mecp2-WT, injected with PBS, control, biol rep 2 Cortex of Mecp2-WT, inj…
GSM9063954 Cortex of Mecp2-WT, injected with PBS, control, biol rep 3 Cortex of Mecp2-WT, inj…
GSM9063955 Cortex of Mecp2-WT, injected with PBS, control, biol rep 4 Cortex of Mecp2-WT, inj…
GSM9063956 Cortex of Mecp2-WT, injected with PBS, control, biol rep 5 Cortex of Mecp2-WT, inj…
GSM9063957 Cortex of Mecp2-WT, injected with PBS, control, biol rep 6 Cortex of Mecp2-WT, inj…
GSM9063958 Cortex of Mecp2-KO, injected with PBS, control, biol rep 1 Cortex of Mecp2-KO, inj…
GSM9063959 Cortex of Mecp2-WT, injected with PBS, control, biol rep 7 Cortex of Mecp2-WT, inj…
GSM9063960 Cortex of Mecp2-KO, injected with PBS, control, biol rep 2 Cortex of Mecp2-KO, inj…
GSM9063961 Cortex of Mecp2-WT, injected with PBS, control, biol rep 8 Cortex of Mecp2-WT, inj…
GSM9063962 Cortex of Mecp2-KO, injected with PBS, control, biol rep 3 Cortex of Mecp2-KO, inj…
GSM9063963 Cortex of Mecp2-WT, injected with PBS, control, biol rep 9 Cortex of Mecp2-WT, inj…
GSM9063964 Cortex of Mecp2-KO, injected with PBS, control, biol rep 4 Cortex of Mecp2-KO, inj…
GSM9063965 Cortex of Mecp2-WT, injected with PBS, control, biol rep 10 Cortex of Mecp2-WT, inj…
GSM9063966 Cortex of Mecp2-WT, injected with PBS, control, biol rep 11 Cortex of Mecp2-WT, inj…
GSM9063967 Cortex of Mecp2-KO, injected with PBS, control, biol rep 5 Cortex of Mecp2-KO, inj…
GSM9063968 Cortex of Mecp2-WT, injected with PBS, control, biol rep 12 Cortex of Mecp2-WT, inj…
GSM9063969 Cortex of Mecp2-WT, injected with PBS, control, biol rep 13 Cortex of Mecp2-WT, inj…
GSM9063970 Cortex of Mecp2-WT, injected with PBS, control, biol rep 14 Cortex of Mecp2-WT, inj…
GSM9063971 Cortex of Mecp2-WT, injected with PBS, control, biol rep 15 Cortex of Mecp2-WT, inj…
GSM9063972 Cortex of Mecp2-WT, injected with PBS, control, biol rep 16 Cortex of Mecp2-WT, inj…
GSM9063973 Cortex of Mecp2-KO, injected with PBS, control, biol rep 6 Cortex of Mecp2-KO, inj…
GSM9063974 Cortex of Mecp2-WT, injected with PBS, control, biol rep 17 Cortex of Mecp2-WT, inj…
GSM9063975 Cortex of Mecp2-WT, injected with PBS, control, biol rep 18 Cortex of Mecp2-WT, inj…
GSM9063976 Cortex of Mecp2-WT, injected with PBS, control, biol rep 19 Cortex of Mecp2-WT, inj…
GSM9063977 Cortex of Mecp2-WT, injected with PBS, control, biol rep 20 Cortex of Mecp2-WT, inj…
GSM9063978 Cortex of Mecp2-WT, injected with PBS, control, biol rep 21 Cortex of Mecp2-WT, inj…
GSM9063979 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 1 Cortex of Mecp2-KO, inj…
GSM9063980 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 2 Cortex of Mecp2-KO, inj…
GSM9063981 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 3 Cortex of Mecp2-KO, inj…
GSM9063982 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 4 Cortex of Mecp2-KO, inj…
GSM9063983 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 5 Cortex of Mecp2-KO, inj…
GSM9063984 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 6 Cortex of Mecp2-KO, inj…
GSM9063985 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 7 Cortex of Mecp2-KO, inj…
GSM9063986 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 8 Cortex of Mecp2-KO, inj…
GSM9063987 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 9 Cortex of Mecp2-KO, inj…
GSM9063988 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 10 Cortex of Mecp2-KO, inj…
GSM9063989 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biol rep 11 Cortex of Mecp2-KO, inj…

+ 97 more — browse all 137 samples with per-sample file links →

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GSE300536 Brain Mecp2 Genetic Dosage and Gene Therapy Shape Multi-omics Signatures and Biomarkers in Rett Syndrome [2] 137 samples shares mecp2, multi-omics, signatures, biomarkers, genetic, therapy, dosage, brain
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