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Hematopoietic loss of Y chromosome activates immune checkpoints to impair senescent cell clearance contributing to renal disease

GSE301560 Mus musculus (mouse) RNA-seq (gene expression) 20 samples Submitted 2025/07/09 Platform GPL34328
At a glance

RNA-seq (gene expression) · mouse · 20 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
20 samples: 6 × Kidney, Control, Animal vs 6 × Kidney, LOY, Animal vs 4 × Kidney, LOY + Control, Animal vs 4 × Kidney, LOY + ABT263, AnimalGroups 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
Hematopoietic loss of Y chromosome activates immune checkpoints and contributes to impaired senescent cell clearance and renal diseaseScience translational medicine · 2025
Summary (written by the submitters)
The accumulation of senescent cells contributes to morbidity and mortality; however, common mechanisms underpinning this age-associated phenomenon remain elusive. Notably, hematopoietic loss of the Y chromosome (LOY) is the most frequently acquired somatic mutation in males, and this condition has been associated with various age-associated diseases and reduced lifespan.
Read the full summary ↓
Therefore, we investigated the role of hematopoietic LOY in promoting cellular senescence, focusing on kidney disease due to its well-documented connection with aging and senescence. Herein, a prospective cohort study revealed that LOY in blood is associated with an increased incidence of kidney diseases. Analyses of transcriptional signatures in human kidneys found that immune cell LOY is enriched in patients with kidney disease and associated with greater levels of cellular senescence. In mice, hematopoietic LOY led to renal dysfunction that was accompanied by senescent cell accumulation in models of kidney injury and advanced age. Accordingly, treatment with a senolytic agent promoted senolysis and preferentially inhibited the progression of renal dysfunction in LOY mice. The hematopoietic LOY condition led to the upregulation of multiple immune inhibitory receptors. Treatment with the combination of antibodies targeting PD-1 and SIRP reduced senescent cell accumulation and rescued the renal pathology conferred by hematopoietic LOY. These data indicate that hematopoietic LOY contributes to pathologic conditions by impairing the clearance of senescent cells through upregulation of immune checkpoint proteins.
Published in
Hematopoietic loss of Y chromosome activates immune checkpoints and contributes to impaired senescent cell clearance and renal disease
Arai Y, Chavkin NW, Arai Y et al. · Science translational medicine 2025 · PMID 40768598 · doi:10.1126/scitranslmed.adv4071
This dataset
Open GSE301560 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 GSE301560_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 PRJNA1285446 and SRA study SRP597892. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40768598) ↗
Study design
6 × Kidney, Control, Animal vs 6 × Kidney, LOY, Animal vs 4 × Kidney, LOY + Control, Animal vs 4 × Kidney, LOY + ABT263, Animal

Supports a between-group comparison across 20 samples.

How we read this: 4 replicated groups read from 20 sample titles; they account for 20 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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