GEO series

Restoration of Spermatogenesis is Dependent on Activation of a SPRY4-ERK Checkpoint Following Germline Stem Cell Damage

GSE318472 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2026/04/22 Platform GPL34290

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: 4 × WT spermatogonia, BU-D10, vs 4 × WT spermatogonia, BU+PD-D10, vs 4 × Spry4 G-KO spermatogonia, BU-D10, vs 4 × Spry4 G-KO spermatogonia, BU+PD-D10,Groups 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: Restoration of spermatogenesis is dependent on activation of a SPRY4-ERK checkpoint following germline stem cell damage†Biology of reproduction · 2026

Summary (written by the submitters)

Mammalian spermatogonial stem cells (SSCs) sustain male fertility through continuous self-renewal and differentiation, leading to the production of haploid spermatozoa throughout adulthood. However, SSCs are vulnerable to genotoxic drugs, and patients receiving chemotherapy face a high risk of germline instability and infertility. The molecular mechanisms and cellular pathways that choreograph SSC recovery after chemotherapeutic insult remain unknown.

Read the full summary ↓

Previously, we identified SPRY4 as an ERK-dependent negative feedback regulator of growth factor signaling that is critical for preservation of stem cell activity in cultured mouse SSCs. Here, we demonstrate that following alkylating agent busulfan (BU)-induced injury in adult mice, germline-specific Spry4 gene deletion (Spry4G-KO) reduces stem cell regeneration with an enhanced genotoxic stress response and differentiation with rapidly enhanced nuclear ERK1/2 activity in undifferentiated (Aundiff) spermatogonia (including SSCs). Genes essential for stem cell maintenance, including Id1 and Cxcl12, were dysregulated by loss of Spry4. Furthermore, the MEK1/2 inhibitor PD0325901, but not mTORC1 inhibitor Rapamycin, was sufficient to promote spermatogonial proliferation in Spry4G-KO testis 10 days post-BU treatment. Notably, the restoration of both spermatogonia pool and fertility was delayed in adult Spry4G-KO males long-term after injury. In summary, germline-specific deletion of Spry4 results in hyper-activation of the MAPK/ERK pathway in Aundiff spermatogonia, reducing spermatogonial genome integrity, unleashing excessive spermatogenesis after germline damage, and ultimately impairing germline regeneration in adult males. Our study indicates an essential role for SPRY4-ERK signaling as a molecular checkpoint in securing SSC recovery upon chemotherapy drug-induced germline damage, revealing how stem cells normally withstand environmental stress.

Published in

Restoration of spermatogenesis is dependent on activation of a SPRY4-ERK checkpoint following germline stem cell damage†

Liu Y, Choi T, Pearson B et al. · Biology of reproduction 2026 · PMID 41852347 · doi:10.1093/biolre/ioag063

This dataset

Open GSE318472 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 GSE318472_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 PRJNA1418800 and SRA study SRP674663. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41852347) ↗

Study design

4 × WT spermatogonia, BU-D10, vs 4 × WT spermatogonia, BU+PD-D10, vs 4 × Spry4 G-KO spermatogonia, BU-D10, vs 4 × Spry4 G-KO spermatogonia, BU+PD-D10,

Supports a between-group comparison across 16 samples.

How we read this: 4 replicated groups read from 16 sample titles; they account for 16 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

GSM9495965 WT spermatogonia, BU-D10, rep1 WT spermatogonia, BU-D1…
GSM9495966 WT spermatogonia, BU-D10, rep2 WT spermatogonia, BU-D1…
GSM9495967 WT spermatogonia, BU-D10, rep3 WT spermatogonia, BU-D1…
GSM9495968 WT spermatogonia, BU-D10, rep4 WT spermatogonia, BU-D1…
GSM9495969 WT spermatogonia, BU+PD-D10, rep1 WT spermatogonia, BU+PD…
GSM9495970 WT spermatogonia, BU+PD-D10, rep2 WT spermatogonia, BU+PD…
GSM9495971 WT spermatogonia, BU+PD-D10, rep3 WT spermatogonia, BU+PD…
GSM9495972 WT spermatogonia, BU+PD-D10, rep4 WT spermatogonia, BU+PD…
GSM9495973 Spry4 G-KO spermatogonia, BU-D10, rep1 Spry4 G-KO spermatogoni…
GSM9495974 Spry4 G-KO spermatogonia, BU-D10, rep2 Spry4 G-KO spermatogoni…
GSM9495975 Spry4 G-KO spermatogonia, BU-D10, rep3 Spry4 G-KO spermatogoni…
GSM9495976 Spry4 G-KO spermatogonia, BU-D10, rep4 Spry4 G-KO spermatogoni…
GSM9495977 Spry4 G-KO spermatogonia, BU+PD-D10, rep1 Spry4 G-KO spermatogon…
GSM9495978 Spry4 G-KO spermatogonia, BU+PD-D10, rep2 Spry4 G-KO spermatogon…
GSM9495979 Spry4 G-KO spermatogonia, BU+PD-D10, rep3 Spry4 G-KO spermatogon…
GSM9495980 Spry4 G-KO spermatogonia, BU+PD-D10, rep4 Spry4 G-KO spermatogon…

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