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Limitations in mitochondrial programming restrain the maturation of human stem cell-derived β cells

GSE270220 Homo sapiens (human) RNA-seq (gene expression) 81 samples Submitted 2025/01/15 Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 81 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
81 samples: 17 conditions, mostly with about 5 replicates eachGroups 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
Limitations in PPAR⍺-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cellsbioRxiv : the preprint server for biology · 2025
Summary (written by the submitters)
Pluripotent stem cell-derived (SC) islets offer a renewable source for β cell replacement for type 1 diabetes, yet functional and metabolic immaturity may limit their long-term therapeutic efficacy. Here, we describe that limitations in mitochondrial transcriptional programming prevent the maturation of SC-β cells. We observe several alterations in SC-islet mitochondria compared to human islets, including reductions in mitochondrial respiration, expression of OXPHOS machinery, and mitochondrial lipid metabolism.
Read the full summary ↓
Surprisingly, these effects were not related to reductions in mitochondrial mass, genome integrity, or structure. Transcriptomic profiling throughout differentiation to SC-islets revealed several unstudied candidates in β cell maturation that regulate programming of mitochondrial oxidative and fatty acid metabolism, including the nuclear receptors PPAR⍺ and PPARγ. Indeed, treatment of SC-islets with WY14643, a potent PPAR⍺ agonist with PPARγ activity, promoted expression of mitochondrial targets, improved insulin secretion, and increased the presence of β cells both in vitro and upon transplantation into immunodeficient mice. Mitochondria are vital to fuel β cell insulin release; however, our studies here revealed the potential for targeting mitochondrial programming to enhance the differentiation and metabolic maturation of SC-β cells.
Published in
Limitations in PPAR⍺-dependent mitochondrial programming restrain the differentiation of human stem cell-derived β cells
Lietzke AC, Walker EM, Bealer E et al. · bioRxiv : the preprint server for biology 2025 · PMID 39211191 · doi:10.1101/2024.07.26.605318
This dataset
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.

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 GSE270220_RAW.tar (it can run to tens of gigabytes).

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.

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 PRJNA1125428 and SRA study SRP514726. Searching any of these in the dataset finder brings you back here.

Study design
17 conditions, mostly with about 5 replicates each
Human Islet ×6 H1,S4 ×6 H1,S5 ×6 H1,S6 ×6 H1,S1 ×5 H1,S2 ×5 Hues8,S1 ×5 Hues8,S2 ×5 +9 more

Supports a between-group comparison across 81 samples.

How we read this: 17 replicated groups read from 81 sample titles; they account for 81 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

+ 41 more — browse all 81 samples with per-sample file links →

Datasets on a similar topic

Search all human RNA-seq datasets in GEO →

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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.