GEO series

Brain Mecp2 Genetic Dosage and Gene Therapy Shape Multi-omics Signatures and Biomarkers in Rett Syndrome [2]

GSE300536 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 GSE300536 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 GSE300536_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 PRJNA1281126 and SRA study SRP594000. 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

GSM9064094 Cortex of Mecp2-KO, non-injected control, biolrep 1 Cortex of Mecp2-KO, non…
GSM9064095 Cortex of Mecp2-KO, non-injected control, biolrep 2 Cortex of Mecp2-KO, non…
GSM9064096 Cortex of Mecp2-WT, injected with PBS, control, biolrep 1 Cortex of Mecp2-WT, inj…
GSM9064097 Cortex of Mecp2-WT, injected with PBS, control, biolrep 2 Cortex of Mecp2-WT, inj…
GSM9064098 Cortex of Mecp2-WT, injected with PBS, control, biolrep 3 Cortex of Mecp2-WT, inj…
GSM9064099 Cortex of Mecp2-WT, injected with PBS, control, biolrep 4 Cortex of Mecp2-WT, inj…
GSM9064100 Cortex of Mecp2-WT, injected with PBS, control, biolrep 5 Cortex of Mecp2-WT, inj…
GSM9064101 Cortex of Mecp2-WT, injected with PBS, control, biolrep 6 Cortex of Mecp2-WT, inj…
GSM9064102 Cortex of Mecp2-KO, injected with PBS, control, biolrep 1 Cortex of Mecp2-KO, inj…
GSM9064103 Cortex of Mecp2-WT, injected with PBS, control, biolrep 7 Cortex of Mecp2-WT, inj…
GSM9064104 Cortex of Mecp2-KO, injected with PBS, control, biolrep 2 Cortex of Mecp2-KO, inj…
GSM9064105 Cortex of Mecp2-WT, injected with PBS, control, biolrep 8 Cortex of Mecp2-WT, inj…
GSM9064106 Cortex of Mecp2-KO, injected with PBS, control, biolrep 3 Cortex of Mecp2-KO, inj…
GSM9064107 Cortex of Mecp2-WT, injected with PBS, control, biolrep 9 Cortex of Mecp2-WT, inj…
GSM9064108 Cortex of Mecp2-KO, injected with PBS, control, biolrep 4 Cortex of Mecp2-KO, inj…
GSM9064109 Cortex of Mecp2-WT, injected with PBS, control, biolrep 10 Cortex of Mecp2-WT, inj…
GSM9064110 Cortex of Mecp2-WT, injected with PBS, control, biolrep 11 Cortex of Mecp2-WT, inj…
GSM9064111 Cortex of Mecp2-KO, injected with PBS, control, biolrep 5 Cortex of Mecp2-KO, inj…
GSM9064112 Cortex of Mecp2-WT, injected with PBS, control, biolrep 12 Cortex of Mecp2-WT, inj…
GSM9064113 Cortex of Mecp2-WT, injected with PBS, control, biolrep 13 Cortex of Mecp2-WT, inj…
GSM9064114 Cortex of Mecp2-WT, injected with PBS, control, biolrep 14 Cortex of Mecp2-WT, inj…
GSM9064115 Cortex of Mecp2-WT, injected with PBS, control, biolrep 15 Cortex of Mecp2-WT, inj…
GSM9064116 Cortex of Mecp2-WT, injected with PBS, control, biolrep 16 Cortex of Mecp2-WT, inj…
GSM9064117 Cortex of Mecp2-KO, injected with PBS, control, biolrep 6 Cortex of Mecp2-KO, inj…
GSM9064118 Cortex of Mecp2-WT, injected with PBS, control, biolrep 17 Cortex of Mecp2-WT, inj…
GSM9064119 Cortex of Mecp2-WT, injected with PBS, control, biolrep 18 Cortex of Mecp2-WT, inj…
GSM9064120 Cortex of Mecp2-WT, injected with PBS, control, biolrep 19 Cortex of Mecp2-WT, inj…
GSM9064121 Cortex of Mecp2-WT, injected with PBS, control, biolrep 20 Cortex of Mecp2-WT, inj…
GSM9064122 Cortex of Mecp2-WT, injected with PBS, control, biolrep 21 Cortex of Mecp2-WT, inj…
GSM9064123 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 1 Cortex of Mecp2-KO, inj…
GSM9064124 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 2 Cortex of Mecp2-KO, inj…
GSM9064125 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 3 Cortex of Mecp2-KO, inj…
GSM9064126 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 4 Cortex of Mecp2-KO, inj…
GSM9064127 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 5 Cortex of Mecp2-KO, inj…
GSM9064128 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 6 Cortex of Mecp2-KO, inj…
GSM9064129 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 7 Cortex of Mecp2-KO, inj…
GSM9064130 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 8 Cortex of Mecp2-KO, inj…
GSM9064131 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 9 Cortex of Mecp2-KO, inj…
GSM9064132 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 10 Cortex of Mecp2-KO, inj…
GSM9064133 Cortex of Mecp2-KO, injected with AAV9-rrt271 1e11, biolrep 11 Cortex of Mecp2-KO, inj…

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

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