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Precise Gene Editing of Pathogenic Lamin A Mutations Corrects Cardiac Disease

GSE308777 Mus musculus (mouse) RNA-seq (gene expression) 18 samples Submitted 2025/09/23 Platform GPL30172

At a glance

RNA-seq (gene expression) · mouse · 18 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: 18 samples: 6 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.

Summary (written by the submitters)

Mutations in the lamin A (LMNA) gene, which encodes the lamin A and C proteins, cause severe human diseases collectively known as laminopathies. These conditions are often devastating and lack effective therapies. In this study, we developed precise base editing (BE) strategies targeting the human LMNA gene variants L35P and R249Q, which cause Congenital Muscular Dystrophy (CMD) and Dilated Cardiomyopathy with Conduction Defects (DCM-CD), respectively.

Read the full summary ↓

Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) carrying the R249Q mutation displayed nuclear aberrations, DNA damage, and abnormal Ca2+ transients. Similarly, L35P iPSC-CMs exhibited abnormal contraction, DNA damage, and reduced lamin A/C protein expression. We also generated novel “humanized” mouse models carrying these pathogenic human mutations. R249Q homozygous mice exhibited cardiac conduction abnormalities, cardiac arrhythmias, and premature death. Mice with the homozygous L35P mutation displayed severe muscle-wasting and reduced lifespan, while heterozygous L35P mice displayed dilated cardiomyopathy (DCM). We developed an adenine base editing (ABE) approach for correcting the R249Q mutation and a cytosine base editing (CBE) strategy for the L35P variant. Precise correction of these mutations in iPSC-CMs successfully rescued all of the in vitro abnormalities. Furthermore, delivery of the BE components using adeno-associated virus (AAV) prevented the pathological phenotypes and extended longevity of mice carrying the LMNA L35P and the R249Q mutations. These results demonstrate the efficacy of ABE and CBE in correcting pathogenic LMNA mutations that cause cardiac disease, highlighting BE as a promising therapeutic approach for human laminopathies.

This dataset

Open GSE308777 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 GSE308777_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 PRJNA1332702 and SRA study SRP624971. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗

Study design

6 conditions, mostly in triplicate

Heart_Ex4_WT ×3 Heart_Ex4_R249Q ×3 Heart_Ex4_corrected ×3 Heart_Ex1_WT ×3 Heart_Ex1_L35P ×3 Heart_Ex1_corrected ×3

Supports a between-group comparison across 18 samples.

How we read this: 6 replicated groups read from 18 sample titles; they account for 18 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

GSM9253000 Heart_Ex4_WT_1 Heart_Ex4_WT
GSM9253001 Heart_Ex4_WT_2 Heart_Ex4_WT
GSM9253002 Heart_Ex4_WT_3 Heart_Ex4_WT
GSM9253003 Heart_Ex4_R249Q_1 Heart_Ex4_R249Q
GSM9253004 Heart_Ex4_R249Q_2 Heart_Ex4_R249Q
GSM9253005 Heart_Ex4_R249Q_3 Heart_Ex4_R249Q
GSM9253006 Heart_Ex4_corrected_1 Heart_Ex4_corrected
GSM9253007 Heart_Ex4_corrected_2 Heart_Ex4_corrected
GSM9253008 Heart_Ex4_corrected_3 Heart_Ex4_corrected
GSM9253009 Heart_Ex1_WT_1 Heart_Ex1_WT
GSM9253010 Heart_Ex1_WT_2 Heart_Ex1_WT
GSM9253011 Heart_Ex1_WT_3 Heart_Ex1_WT
GSM9253012 Heart_Ex1_L35P_1 Heart_Ex1_L35P
GSM9253013 Heart_Ex1_L35P_2 Heart_Ex1_L35P
GSM9253014 Heart_Ex1_L35P_3 Heart_Ex1_L35P
GSM9253015 Heart_Ex1_corrected_1 Heart_Ex1_corrected
GSM9253016 Heart_Ex1_corrected_2 Heart_Ex1_corrected
GSM9253017 Heart_Ex1_corrected_3 Heart_Ex1_corrected

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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.