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TCA cycle rewiring underpins histone acetylation sourcing and cell-fate transitions during exit from naive pluripotency

GSE294457 Mus musculus (mouse) RNA-seq (gene expression) 12 samples Submitted 2026/04/21 Platform GPL30172
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: 3 × control (negative/scramble) ESCs vs 3 × repression of all three Pcx, Me1 and Me2 (3xKD) in ESCs vs 3 × control (negative/scramble) EpiLCs day 2 vs 3 × repression of all three Pcx, Me1 and Me2 (3xKD) in EpiLCs day 2Groups 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
TCA cycle rewiring underpins histone acetylation sourcing and cell-fate transitions during exit from naive pluripotencyCell stem cell · 2026
Summary (written by the submitters)
Metabolism has emerged as a crucial regulator of development and stem cell epigenome. This coupling is particularly evident during the in vitro exit from naïve pluripotency. However, our understanding of the dynamic metabolic rewiring at this developmental stage remains rudimentary. In this study, we reconstruct intracellular metabolite routings in pre- and post-implantation mouse embryos and their dynamic stem cell models.
Read the full summary ↓
Our findings reveal that, instead of a simple TCA cycle shutdown, there is spatio-temporally programmed TCA cycle rewiring at implantation. Focusing on the pluripotency spectrum, we identify pyruvate as a key metabolic nexus. Indeed, pyruvate carboxylase and malic enzyme activity is essential for maintaining a balanced metabolic and transcriptional state as well as timely exit from naïve pluripotency. Additionally, we discover that formative and primed pluripotent cells exhibit increased glutamine uptake, reduced oxidative TCA activity, and reciprocal reductive glutamine metabolism. This metabolic rewiring supports increased histone acetylation turnover, primarily using glutamine as a carbon source, supplemented by pyruvate cycling. Thus, we uncover diverse nutrient strategies that are functionally coupled to epigenome programming and dynamic pluripotency cell state transitions at the time of implantation.
Published in
TCA cycle rewiring underpins histone acetylation sourcing and cell-fate transitions during exit from naive pluripotency
Kafkia E, Pladevall-Morera D, Argemi-Muntadas L et al. · Cell stem cell 2026 · PMID 42034059 · doi:10.1016/j.stem.2026.04.004
This dataset
Open GSE294457 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 GSE294457_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 PRJNA1249489 and SRA study SRP577784. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 42034059) ↗
Study design
3 × control (negative/scramble) ESCs vs 3 × repression of all three Pcx, Me1 and Me2 (3xKD) in ESCs vs 3 × control (negative/scramble) EpiLCs day 2 vs 3 × repression of all three Pcx, Me1 and Me2 (3xKD) in EpiLCs day 2

Supports a between-group comparison across 12 samples.

How we read this: 4 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
Datasets on a similar topic

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