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Elevated brain manganese induces motor disease by up-regulating the kynurenine pathway of tryptophan metabolism

GSE292533 Mus musculus (mouse) RNA-seq (gene expression) 44 samples Submitted 2025/03/20 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 44 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
44 samples: 44 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.
Paper
Elevated brain manganese induces motor disease by upregulating the kynurenine pathway of tryptophan metabolismProceedings of the National Academy of Sciences of the United States of America · 2025
Summary (written by the submitters)
Elevated brain levels of the essential metals manganese (Mn), copper, or iron induce motor disease. However, mechanisms of metal-induced motor disease are unclear and treatments are lacking. Elucidating the mechanisms of Mn-induced motor disease is particularly important because occupational and environmental Mn overexposure is a global public health problem.
Read the full summary ↓
To address this, here we combined unbiased transcriptomics and metabolomics with functional studies in a mouse model of human environmental Mn exposure. Transcriptomics unexpectedly revealed that Mn exposure up-regulated expression of metabolic pathways in the brain and liver. Notably, genes in the kynurenine pathway of tryptophan metabolism, which produces neuroactive metabolites that impact neurological function, were up-regulated by Mn. Subsequent unbiased metabolomics revealed that Mn treatment altered kynurenine pathway metabolites in the brain and liver. Functional experiments then demonstrated that pharmacological inhibition of the first and rate-limiting step of the kynurenine pathway fully rescued Mn-induced motor deficits. Finally, elevated Mn directly activates hypoxia-inducible factor (HIF) transcription factors, and additional mechanistic assays identified a role for HIF1, but not HIF2, in regulating expression of hepatic kynurenine pathway genes under physiological or Mn exposure conditions, suggesting that Mn-induced HIF1 activation may contribute to the dysregulation of the kynurenine pathway in Mn toxicity. These findings (1) identify the upregulation of the kynurenine pathway by elevated Mn as a fundamental mechanism of Mn-induced motor deficits; (2) provide a pharmacological approach to treat Mn-induced motor disease; and (3) should broadly advance understanding of the general principles underlying neuromotor deficits caused by metal toxicity.
Published in
Elevated brain manganese induces motor disease by upregulating the kynurenine pathway of tryptophan metabolism
Warden AS, Sharma N, Hutchens S et al. · Proceedings of the National Academy of Sciences of the United States of America 2025 · PMID 40244671 · doi:10.1073/pnas.2423628122
This dataset
Open GSE292533 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 GSE292533_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 PRJNA1239916 and SRA study SRP571998. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40244671) ↗
Study design
44 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 44 sample titles: 44 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

+ 4 more — browse all 44 samples with per-sample file links →

Datasets on a similar topic

Search all mouse RNA-seq datasets in GEO →

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