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Metabolic adaptations direct cell fate during tissue regeneration [shOGDH_Mice_RNA-seq]

GSE293286 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2025/04/02 Platform GPL17021
At a glance

RNA-seq (gene expression) · mouse · 12 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
12 samples: 6 × shRen_Mouse vs 6 × shOgdh_MouseGroups 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
Metabolic adaptations direct cell fate during tissue regenerationNature · 2025
Summary (written by the submitters)
Although cell fate specification is generally attributed to transcriptional regulation, emerging data also indicate a role for molecules linked with intermediary metabolism. For example, α-ketoglutarate (αKG), which fuels energy production and biosynthetic pathways in the tricarboxylic acid (TCA) cycle, is also a co-factor for chromatin-modifying enzymes1-3.
Read the full summary ↓
Nevertheless, whether TCA cycle metabolites regulate cell fate during tissue homeostasis and regeneration remains unexplored. In the intestine, we discovered unexpectedly heterogeneous expression of TCA cycle enzymes, with αKG dehydrogenase complex components4-6 upregulated in the absorptive lineage and downregulated in the secretory lineage. Using genetically modified mouse models and organoids, we demonstrated a dual, lineage-specific role for 2-oxoglutarate dehydrogenase (OGDH), the enzymatic subunit of αKG dehydrogenase complex. In the absorptive lineage, OGDH is upregulated by Hnf4 transcription factors to maintain the bioenergetic and biosynthetic needs of enterocytes. In the secretory lineage, OGDH is downregulated through a process that, when modeled, increases αKG levels and stimulates secretory cell differentiation. Consistent with this, in murine colitis models with impaired secretory cell number and maturation, OGDH inhibition or αKG supplementation reversed these impairments and promoted tissue healing. Hence, OGDH dependency is lineage-specific, and its regulation helps direct cell fate, offering insights for targeted therapies in regenerative medicine.
Published in
Metabolic adaptations direct cell fate during tissue regeneration
Chaves-Perez A, Millman SE, Janaki-Raman S et al. · Nature 2025 · PMID 40500453 · doi:10.1038/s41586-025-09097-6
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 GSE293286_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 PRJNA1243911 and SRA study SRP574815. Searching any of these in the dataset finder brings you back here.

Study design
6 × shRen_Mouse vs 6 × shOgdh_Mouse

Supports a between-group comparison across 12 samples.

How we read this: 2 replicated groups read from 12 sample titles; they account for 12 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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