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A humanized neuronal model system reveals key roles for the trace element manganese in neuronal endocytosis, calcium flux and mitochondrial bioenergetics

GSE266943 Homo sapiens (human) RNA-seq (gene expression) 48 samples Submitted 2025/05/01 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 48 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
48 samples: 16 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.
Paper
An iPSC-derived neuronal model reveals manganese's role in neuronal endocytosis, calcium flux and mitochondrial bioenergeticsiScience · 2025
Summary (written by the submitters)
Manganese (Mn) is an essential trace metal that is necessary for life. Its duality as both a crucial micronutrient and potential neurotoxicant necessitates tight control of intracellular and extracellular Mn levels. Dysregulation of Mn is implicated in a broad range of human diseases, from neurodevelopmental sequelae related to Mn levels in drinking water, to acquired forms of manganism, rare inherited Mn transportopathies and more common disorders such as Parkinson’s and Alzheimer’s disease.
Read the full summary ↓
Despite the clear association between Mn dysregulation and neurodevelopmental or neurodegenerative diseases, the underlying cellular mechanisms that govern neuropathology remain poorly understood. We established a humanised midbrain neuronal system to better understand the neuronal sequelae of Mn dysregulation. By integrating transcriptomic and functional approaches, we show that Mn dyshomeostasis leads to dysregulation of key cellular pathways that are crucial to normal neuronal function, including defects in mitochondrial bioenergetics, calcium signalling, endocytosis, and glycosylation, as well as cellular stress and early neurodegeneration. Our humanized model has enhanced understanding of the role of Mn in the human brain, and the consequences of both acquired and genetic disorders associated with Mn dysregulation. Better understanding of these underlying pathophysiological processes will identify potential targets for future therapeutic intervention.
Published in
An iPSC-derived neuronal model reveals manganese's role in neuronal endocytosis, calcium flux and mitochondrial bioenergetics
Budinger D, Alhaque S, González-Méndez R et al. · iScience 2025 · PMID 40917882 · doi:10.1016/j.isci.2025.113311
This dataset
Open GSE266943 in finder → Find more human 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 GSE266943_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 PRJNA1108326 and SRA study SRP505965. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40917882) ↗
Study design
16 conditions, mostly in triplicate
mDA neurons, control 1, basal, ×3 mDA neurons, SLC39A14 patient 1, basal, ×3 mDA neurons, SLC39A14 patient 2, basal, ×3 mDA neurons, SLC39A8 patient 1, basal, ×3 mDA neurons, SLC39A8 patient 2, basal, ×3 mDA neurons, SLC30A10 patient 1, basal, ×3 mDA neurons, SLC30A10 patient 2, basal, ×3 mDA neurons, control 1, Mn treated, ×3 +10 more

Supports a case/control comparison: 36 samples read as cases, 6 as controls.

How we read this: 16 replicated groups read from 48 sample titles; they account for 46 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

+ 8 more — browse all 48 samples with per-sample file links →

Datasets on a similar topic

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