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3D Chromatin organization of signal-induced specific enhancers safeguards early ESC differentiation by promoting cluster gene expression [RNA-seq]

GSE276734 Mus musculus (mouse) Single-cell RNA-seq 21 samples Submitted 2026/04/20 Platform GPL34328
At a glance

Single-cell RNA-seq · mouse · 21 samples

What it is
Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Mus musculus (mouse)
Samples
21 samples: 7 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.
Summary (written by the submitters)
Cells undergo fate transformation in response to external signaling stimuli, a process that depends on the precise expression of specific genes, but the intrinsic regulatory mechanisms remain largely unclear. Here, by integrating bulk RNA sequencing, single-cell RNA sequencing, 4D-SmartDIA quantitative proteomics data, and a CRISPR/Cas9-mediated RA receptor deletion model, we find that RA signaling-induced early ESC differentiation is multilineage.
Read the full summary ↓
During early ESC differentiation, in the context of attenuated and enhanced RA signaling, we identified Cyp26 and HoxB cluster genes as its direct downstream targets. Upon activation of RA signaling, RA receptors induce new specific enhancers in the proximal/distal regions of cluster gene loci, whereas inhibition of RA signaling significantly reduces proximal/distal enhancer activity, chromatin accessibility and cluster gene expression. Mechanistically, we found that proximal/distal enhancers form specific chromatin loops with cluster gene loci under RA induction, and RA receptor deletion significantly reduces these chromatin interactions. Knockout of the proximal/distal enhancers inhibits cluster gene expression, thereby further disrupting RA-induced early ESC differentiation. In summary, our findings reveal an insightful mechanism underlying the signal-induced specific 3D genomic structure and cluster gene expression critical for early ESC fate transitions.
This dataset
Open GSE276734 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 GSE276734_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1158775 and SRA study SRP531569. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗
Study design
7 conditions, mostly in triplicate
ESC-RA-0h-bulkRNA ×3 ESC-NoRA12h-bulkRNA ×3 ESC-RA12h-bulkRNA ×3 ESC-NoRA24h-bulkRNA ×3 ESC-RA24h-bulkRNA ×3 Cyp26a1-WT ×3 Cyp26a1-KO ×3

Supports a between-group comparison across 21 samples.

How we read this: 7 replicated groups read from 21 sample titles; they account for 21 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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