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Nuclear compression-mediated DNA damage drives ATR-dependent Lamin expression and mouse ESC differentiation

GSE262150 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2025/09/01 Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 16 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: 16 samples: 14 distinct titles, 1 of them repeatedGroups 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: Nuclear compression-mediated DNA damage drives ATR-dependent Lamin expression and mouse ESC differentiationNucleic acids research · 2025

Summary (written by the submitters)

Embryonic stem cells (ESCs) which are susceptible to DNA damage depend on a robust and highly efficient DNA damage response (DDR) mechanism for their survival. However, the implications of physical force-mediated DNA damage on ESC fate remains unclear. Here we assessed the importance of DNA damage in ESC differentiation by culturing mouse ESCs (mESCs) on substrates of varying stiffness, which has been shown to induce stem cell differentiation.

Read the full summary ↓

We show that stiffness-dependent mESC spreading induces DNA damage through nuclear compression that leads to loss of pluripotency, expression of Lamin A/C and germline markers. DNA damage and induction of Lamin A/C are observed in the presence of differentiating agents, as well as during mESC differentiation on cell derived matrices, identifying DNA damage as an early event in differentiation. Differentiation was also associated with reduction of DNA damage and activation of the DDR factor – ATR. While ATR is typically known to play roles in DDR pathway, its role during stiffness-mediated nuclear compression and mESC differentiation is unknown. Nuclear enrichment of activated ATR on stiff substrates and reduction of Lamin A/C expression due to ATR inhibition suggests that mESC differentiation is driven by nuclear compression-mediated DNA damage and involves ATR-dependent modulation of Lamin A/C.

Published in

Nuclear compression-mediated DNA damage drives ATR-dependent Lamin expression and mouse ESC differentiation

Roy T, Ghosh S, Piplani N et al. · Nucleic acids research 2025 · PMID 40923769 · doi:10.1093/nar/gkaf852

This dataset

Open GSE262150 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 GSE262150_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 PRJNA1090477 and SRA study SRP497001. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40923769) ↗

Study design

14 distinct titles, 1 of them repeated

mESC, LIF, S ×3

How we read this: Read from 16 sample titles: 14 distinct titles with little repetition. 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

GSM8158678 mESC, LIF, S1
GSM8158679 mESC, LIF, S2
GSM8158680 mESC, LIF, S3
GSM8158681 mESC, 0.6kPa, 3h
GSM8158682 mESC, 0.6kPa, 6h
GSM8158683 mESC, 0.6kPa, 24h
GSM8158684 mESC, 0.6kPa, 72h
GSM8158685 mESC, 4kPa, 3h
GSM8158686 mESC, 4kPa, 6h
GSM8158687 mESC, 4kPa, 24h
GSM8158688 mESC, 4kPa, 72h
GSM8158689 mESC, 33kPa, 3h
GSM8158690 mESC, 33kPa, 6h
GSM8158691 mESC, 33kPa, 24h
GSM8158692 mESC, 33kpa, 72h
GSM8158693 mESC, 0.6kPa, Etoposide

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