GEO series

p16-expressing microglia and endothelial cells promote tauopathy and neurovascular abnormalities in PS19 mice

GSE294816 Mus musculus (mouse) RNA-seq (gene expression) 16 samples Submitted 2025/04/30 Platform GPL21493

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 × wildtype vs 4 × p16KO vs 4 × PS19 vs 4 × PS19_p16KOGroups 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: p16-expressing microglia and endothelial cells promote tauopathy and neurovascular abnormalities in PS19 miceNeuron · 2025

Summary (written by the submitters)

Cellular senescence is characterized by irreversible cell cycle exit, acquisition of a pro-inflammatory secretory phenotype, macromolecular damage, and deregulated metabolism. Senescent cells have been implicated in many age-related diseases, including neurodegenerative disease. We have previously demonstrated that selective elimination of senescent cells, both pharmacologically and genetically, prevents neurodegenerative disease phenotypes in tau (MAPTP301S;PS19) mutant mice.

Read the full summary ↓

Here, we show that genetically knocking out the senescence mediator p16Ink4a, a cyclin-dependent kinase inhibitor, is sufficient to attenuate senescence signatures in PS19 mice. Neurodegenerative disease phenotypes dependent on senescent cell accumulation, including neuroinflammation, phosphorylated tau burden, neurodegeneration, and cognitive impairment were blunted in the absence of p16Ink4a. Additionally, we found that PS19 mice display altered neurovascular features—including vessel dilation, increased vessel density, deregulated endothelial cell extracellular matrix, and astrocytic endfoot depolarization—which were also attenuated when p16Ink4a was knocked out. Finally, we utilized a cell-type specific knockout of p16Ink4a to show that p16Ink4a deletion in endothelial cells and microglia alone attenuates many of the same tau-dependent phenotypes as whole-body knockout of p16Ink4a. Taken together, these results indicate that onset and progression of neurodegenerative disease in PS19 mice is driven, at least in part, by p16Ink4a expressing endothelial cells and microglia.

Published in

p16-expressing microglia and endothelial cells promote tauopathy and neurovascular abnormalities in PS19 mice

Graves SI, Meyer CF, Jeganathan KB et al. · Neuron 2025 · PMID 40381614 · doi:10.1016/j.neuron.2025.04.020

This dataset

Open GSE294816 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 GSE294816_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 PRJNA1251640 and SRA study SRP579155. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40381614) ↗

Study design

4 × wildtype vs 4 × p16KO vs 4 × PS19 vs 4 × PS19_p16KO

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

GSM8921758 wildtype_1 wildtype
GSM8921759 wildtype_2 wildtype
GSM8921760 wildtype_3 wildtype
GSM8921761 wildtype_4 wildtype
GSM8921762 p16KO_1 p16KO
GSM8921763 p16KO_2 p16KO
GSM8921764 p16KO_3 p16KO
GSM8921765 p16KO_4 p16KO
GSM8921766 PS19_1 PS19
GSM8921767 PS19_2 PS19
GSM8921768 PS19_3 PS19
GSM8921769 PS19_4 PS19
GSM8921770 PS19_p16KO_1 PS19_p16KO
GSM8921771 PS19_p16KO_2 PS19_p16KO
GSM8921772 PS19_p16KO_3 PS19_p16KO
GSM8921773 PS19_p16KO_4 PS19_p16KO

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