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Tissue-specific expression of Drp1 transcript variants

GSE308731 Homo sapiens (human) RNA-seq (gene expression) 22 samples Submitted 2025/10/01 Platform GPL26624Platform GPL26167
At a glance

RNA-seq (gene expression) · human · 22 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
22 samples: 9 conditions, mostly in duplicateGroups 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)
Dynamin-related protein 1 (Drp1, encoded by DNM1L) is a key regulator of mitochondrial fission, yet its functional role remains controversial, likely due to isoform-specific effects arising from alternative splicing. Conventional short-read RNA sequencing complicates the characterization of full-length isoforms, limiting our understanding of their biological significance.
Read the full summary ↓
To resolve this, we applied a targeted long-read sequencing approach to capture full-length DNM1L transcripts in primary human left ventricle and iPSC-derived cardiomyocytes. We recovered the complete spectrum of annotated isoforms and found broadly conserved expression patterns, with isoforms 1-4 expressed most abundantly. Recombinant protein assays further revealed that isoform abundance does not directly predict enzymatic activity, emphasizing the need for combined expression and functional analyses. Extending this framework to mouse, we profiled Dnm1l isoforms across six tissues (brain, heart, skeletal muscle, lung, kidney, and spleen) using the same long-read pipeline. All annotated isoforms were recovered, with distinct tissue-enriched expression patterns. Notably, several isoforms displayed strong tissue specificity, with subsets preferentially expressed in brain, heart, or skeletal muscle, suggesting specialized regulatory roles in mitochondrial dynamics. Functional rescue experiments in Drp1-knockout mouse embryonic fibroblasts revealed isoform-dependent differences in mitochondrial fission activity. Isoforms lacking the A-insert within the GTPase domain (e.g., isoforms b and d) robustly restored mitochondrial fragmentation, whereas the canonical brain-enriched isoform (isoform e) and a muscle-enriched isoform (isoform o) exhibited only partial rescue. These results indicate that inclusion of exons 2 and 3 may negatively regulate Drp1 fission activity. Together, our work establishes a cross-species atlas of DNM1L/Dnm1l isoforms, integrating long-read transcriptomics with functional assays. We demonstrate that Drp1 isoform diversity is tightly linked to tissue identity and that structural differences among isoforms critically shape mitochondrial fission activity, offering new insights into the pathophysiology of Drp1 in human health and disease.
This dataset
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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 GSE308731_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 PRJNA1332620 and SRA study SRP624545. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
9 conditions, mostly in duplicate
Left Ventricle ×4 CERA cardiomyocyte ×3 CL2 cardiomyocyte ×3 Brain ×2 Lung ×2 Spleen ×2 Heart ×2 Kidney ×2 +1 more

Supports a between-group comparison across 22 samples.

How we read this: 9 replicated groups read from 22 sample titles; they account for 22 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
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