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In vivo chemical reprogramming is associated with a toxic accumulation of lipid droplets hindering rejuvenation

GSE300625 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2026/06/22 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 20 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
20 samples: 6 × 7c, liver, vs 6 × 7c, kidney, vs 4 × control (vehicle), liver, vs 4 × control (vehicle), kidney,Groups 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.
Paper
In Vivo Chemical Reprogramming Is Associated With a Toxic Accumulation of Lipid Droplets Hindering RejuvenationAging cell · 2026
Summary (written by the submitters)
Partial reprogramming has emerged as a promising strategy to reset the epigenetic landscape of aged cells towards more youthful profiles. Recent advancements have included the development of chemical reprogramming cocktails that can lower the epigenetic and transcriptomic age of cells and upregulate mitochondrial biogenesis and oxidative phosphorylation.
Read the full summary ↓
However, the ability of these cocktails to affect biological age in a mammalian aging model has yet to be tested. Here, we have characterized the effects of partial chemical reprogramming on mitochondrial structure and function in aged mouse fibroblasts and tested its in vivo efficacy in genetically diverse male UM-HET3 mice. This approach increases the size of mitochondria, alters cristae morphology, causes an increased fusing of mitochondrial networks, and speeds up movement velocity. At lower doses, the chemical reprogramming cocktail can be safely administered to middle-aged mice using implantable osmotic pumps, albeit with no effect on the transcriptomic age of kidney or liver tissues and only a modest effect on the expression of OXPHOS complexes. However, at higher doses, the cocktail causes a drastic reduction in body weight necessitating euthanasia. In the livers and kidneys of these animals, we observe significant increases in lipid droplet accumulation, as well as changes in mitochondrial morphology in the livers that are associated with mitochondrial stress. Thus, partial chemical reprogramming may induce mitochondrial stress and lead to significant lipid accumulation, which may cause toxicity and hinder the rejuvenation of cells and tissues in aged mammals.
Published in
In Vivo Chemical Reprogramming Is Associated With a Toxic Accumulation of Lipid Droplets Hindering Rejuvenation
Mitchell W, de Magalhães CG, Tyshkovskiy A et al. · Aging cell 2026 · PMID 41589348 · doi:10.1111/acel.70390
This dataset
Open GSE300625 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 GSE300625_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 PRJNA1281576 and SRA study SRP594244. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41589348) ↗
Study design
6 × 7c, liver, vs 6 × 7c, kidney, vs 4 × control (vehicle), liver, vs 4 × control (vehicle), kidney,

Supports a between-group comparison across 20 samples.

How we read this: 4 replicated groups read from 20 sample titles; they account for 20 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
Datasets on a similar topic

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