GEO series

Single-cell multiome profiling reveals neuronal bias of modulatory role of MeCP2 phosphorylation

GSE333915 Mus musculus (mouse) Single-cell RNA-seq 18 samples Submitted 2026/07/03 Platform GPL34328

At a glance

Single-cell RNA-seq · mouse · 18 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart.
Organism: Mus musculus (mouse)
Samples: 18 samples: 18 samples, each with a distinct title — no replicated groupsGroups 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)

MeCP2 is subject to many post-translational modifications, such as phosphorylation, in response to diverse stimuli. Several MeCP2 phosphorylation sites have been identified and studied individually. However, the combinatorial effect of phosphorylation at multiple sites has not been directly examined.

Read the full summary ↓

Building on previous studies characterizing single mutations of MeCP2 phosphorylation sites, we created a mouse model carrying two mutations, serine 80 to alanine and serine 421 to glutamic acid (S80A;S421E, or A;E), in which the MeCP2 protein phosphorylation is fixed in a state observed in active neurons. A battery of behavioral tests was conducted to characterize the functional outcomes at the whole animal level, followed by two independent single-cell/nuclei level multiome profiling assays to characterize altered molecular pathways, and regulatory pattern biased towards glutamatergic neurons on both transcription and chromatin level. While integrated analysis of the multi-dimensional datasets identified cell-type specific molecular targets regulated by MeCP2 phosphorylation, the spatially resolved transcription profiling offered an orthogonal platform for target validation and provided additional information from spatial perspective. Together, results from this study revealed that the combinatorial effect of MeCP2 S80 and S421 phosphorylation is not merely synergistic, and the regulatory is biased towards glutamatergic excitatory neurons. More importantly, our study is the first to explore the single-cell multiomics profile changes in a MeCP2 phosphor mutant model and link it to the functional outcomes.

This dataset

Open GSE333915 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 GSE333915_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1473195 and SRA study SRP705771. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

18 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 18 sample titles: 18 distinct titles with little repetition. 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

GSM9777338 snMultiome, Mouse hippocampus, Mecp2 S80A;S421E, animal 1, GEX
GSM9777339 snMultiome, Mouse hippocampus, Mecp2 S80A;S421E, animal 2, GEX
GSM9777340 snMultiome, Mouse hippocampus, Mecp2 S80A;S421E, animal 3, rep 1, GEX
GSM9777341 snMultiome, Mouse hippocampus, Mecp2 S80A;S421E, animal 3, rep 2, GEX
GSM9777342 snMultiome, Mouse hippocampus, WT, animal 1, GEX
GSM9777343 snMultiome, Mouse hippocampus, WT, animal 2, GEX
GSM9777344 snMultiome, Mouse hippocampus, WT, animal 3, rep 1, GEX
GSM9777345 snMultiome, Mouse hippocampus, WT, animal 3, rep 2, GEX
GSM9777346 snMultiome, Mouse hippocampus, WT, animal 3, rep 3, GEX
GSM9777347 snMultiome, Mouse hippocampus, Mecp2 S80A;S421E, animal 1, ATAC
GSM9777348 snMultiome, Mouse hippocampus, Mecp2 S80A;S421E, animal 2, ATAC
GSM9777349 snMultiome, Mouse hippocampus, Mecp2 S80A;S421E, animal 3, rep 1, ATAC
GSM9777350 snMultiome, Mouse hippocampus, Mecp2 S80A;S421E, animal 3, rep 2, ATAC
GSM9777351 snMultiome, Mouse hippocampus, WT, animal 1, ATAC
GSM9777352 snMultiome, Mouse hippocampus, WT, animal 2, ATAC
GSM9777353 snMultiome, Mouse hippocampus, WT, animal 3, rep 1, ATAC
GSM9777354 snMultiome, Mouse hippocampus, WT, animal 3, rep 2, ATAC
GSM9777355 snMultiome, Mouse hippocampus, WT, animal 3, rep 3, ATAC

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