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A non-canonical bivalent gene Wfdc15a controls spermatogenic protease and immune homeostasis

GSE254564 Mus musculus (mouse) RNA-seq (gene expression) 13 samples Submitted 2024/09/02 Platform GPL24247
At a glance

RNA-seq (gene expression) · mouse · 13 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
13 samples: 3 × Wfdc15a testis, WT2, vs 3 × Wfdc15a testis, Het2, vs 3 × Wfdc15a testis, KO1, vs 3 × Wfdc15a testis, KO2,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
The non-canonical bivalent gene Wfdc15a controls spermatogenic protease and immune homeostasisDevelopment (Cambridge, England) · 2024
Summary (written by the submitters)
Male infertility can be caused by chromosomal abnormalities, mutations, and epigenetic defects. Epigenetic modifiers pre-program hundreds of spermatogenic genes in spermatogonial stem cells (SSCs) for expression later in spermatids, but it remains mostly unclear whether and how those genes are involved in fertility. Here, we report that Wfdc15a, a WFDC family protease inhibitor pre-programmed by KMT2B, is essential for spermatogenesis.
Read the full summary ↓
We found that Wfdc15a is a non-canonical bivalent gene carrying both H3K4me3 and facultative H3K9me3 in SSCs but is later activated along with the loss of H3K9me3 and acquisition of H3K27ac during meiosis. We show that WFDC15A deficiency causes defective spermiogenesis at the beginning of spermatid elongation. Notably, depletion of WFDC15A causes substantial disturbance of the testicular protease-antiprotease network and leads to an orchitis-like inflammatory response associated with TNFa expression in round spermatids. Together, our results reveal a unique epigenetic program regulating innate immunity crucial for fertility.
Published in
The non-canonical bivalent gene Wfdc15a controls spermatogenic protease and immune homeostasis
Tomizawa SI, Fellows R, Ono M et al. · Development (Cambridge, England) 2024 · PMID 39222051 · doi:10.1242/dev.202834
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 GSE254564_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 PRJNA1071058 and SRA study SRP486818. Searching any of these in the dataset finder brings you back here.

Study design
3 × Wfdc15a testis, WT2, vs 3 × Wfdc15a testis, Het2, vs 3 × Wfdc15a testis, KO1, vs 3 × Wfdc15a testis, KO2,

Supports a between-group comparison across 12 samples.

How we read this: 4 replicated groups read from 13 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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