GEO series

A phosphorylation switch within the Mediator subunit MED15 controls cellular senescence and cognitive decline

GSE285138 Mus musculus (mouse) RNA-seq (gene expression) 24 samples Submitted 2025/08/27 Platform GPL24676Platform GPL24247

At a glance

RNA-seq (gene expression) · mouse · 24 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: 24 samples: 8 conditions, mostly in triplicateGroups 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: A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive declineCell discovery · 2025

Summary (written by the submitters)

A hallmark of aging is chronic systemic inflammation, which is exacerbated by the hypersecretory aging phenotype known as the senescence-associated secretory phenotype (SASP). How the SASP is initiated to accelerate tissue inflammation and aging is an outstanding question in ageing biology. Here, we showed that phosphorylation of the mediator subunit MED15 at T603 is able to control the SASP and aging.

Read the full summary ↓

Transforming growth factor-β (TGFβ) selectively induces CDK1-mediated MED15 T603 phosphorylation to control SASP gene expression. The MED15 T603 dephosphorylated mutant (T603A) inhibits the SASP and cell senescence, whereas the T603 phosphorylation-mimicking mutant (T603D) has the opposite effect. Mechanistically, forkhead box protein A1 (FOXA1) preferentially binds to unphosphorylated but not phosphorylated MED15 at T603 to suppress SASP gene expression. Notably, aging mice harboring dephosphorylated mutation in this phosphosite exhibit improved learning and memory through the attenuation of the SASP across tissues. Overall, our study indicates that MED15 T603 phosphorylation serves as a control switch for SASP production, which underlies tissue aging and cognitive decline and provides a novel target for age-related pathology.

Published in

A phosphorylation switch in the Mediator MED15 controls cellular senescence and cognitive decline

Li H, Zheng Y, Yuan C et al. · Cell discovery 2025 · PMID 40825935 · doi:10.1038/s41421-025-00820-1

This dataset

Open GSE285138 in finder → Find more 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 GSE285138_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 PRJNA1201231 and SRA study SRP553068. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 40825935) ↗

Study design

8 conditions, mostly in triplicate

WT HaCaT, TGFβ-0h, RNA-seq, ×3 WT HaCaT, TGFβ-3h, RNA-seq, ×3 MED15 T603A HaCaT, TGFβ-0h, RNA-seq, ×3 MED15 T603A HaCaT, TGFβ-3h, RNA-seq, ×3 WT MCF7, TGFβ-0h, RNA-seq, ×3 MED15 T603D MCF7, TGFβ-0h, RNA-seq, ×3 WT C57 mouse hippocamous tissue, RNA-seq, ×3 MED15 T604A C57 mouse hippocamous tissue, RNA… ×3

Supports a between-group comparison across 24 samples.

How we read this: 8 replicated groups read from 24 sample titles; they account for 24 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

GSM8697150 WT HaCaT, TGFβ-0h, RNA-seq, rep1 WT HaCaT, TGFβ-0h, RNA-…
GSM8697151 WT HaCaT, TGFβ-0h, RNA-seq, rep2 WT HaCaT, TGFβ-0h, RNA-…
GSM8697152 WT HaCaT, TGFβ-0h, RNA-seq, rep3 WT HaCaT, TGFβ-0h, RNA-…
GSM8697153 WT HaCaT, TGFβ-3h, RNA-seq, rep1 WT HaCaT, TGFβ-3h, RNA-…
GSM8697154 WT HaCaT, TGFβ-3h, RNA-seq, rep2 WT HaCaT, TGFβ-3h, RNA-…
GSM8697155 WT HaCaT, TGFβ-3h, RNA-seq, rep3 WT HaCaT, TGFβ-3h, RNA-…
GSM8697156 MED15 T603A HaCaT, TGFβ-0h, RNA-seq, rep1 MED15 T603A HaCaT, TGFβ…
GSM8697157 MED15 T603A HaCaT, TGFβ-0h, RNA-seq, rep2 MED15 T603A HaCaT, TGFβ…
GSM8697158 MED15 T603A HaCaT, TGFβ-0h, RNA-seq, rep3 MED15 T603A HaCaT, TGFβ…
GSM8697159 MED15 T603A HaCaT, TGFβ-3h, RNA-seq, rep1 MED15 T603A HaCaT, TGFβ…
GSM8697160 MED15 T603A HaCaT, TGFβ-3h, RNA-seq, rep2 MED15 T603A HaCaT, TGFβ…
GSM8697161 MED15 T603A HaCaT, TGFβ-3h, RNA-seq, rep3 MED15 T603A HaCaT, TGFβ…
GSM8697162 WT MCF7, TGFβ-0h, RNA-seq, rep1 WT MCF7, TGFβ-0h, RNA-s…
GSM8697163 WT MCF7, TGFβ-0h, RNA-seq, rep2 WT MCF7, TGFβ-0h, RNA-s…
GSM8697164 WT MCF7, TGFβ-0h, RNA-seq, rep3 WT MCF7, TGFβ-0h, RNA-s…
GSM8697165 MED15 T603D MCF7, TGFβ-0h, RNA-seq, rep1 MED15 T603D MCF7, TGFβ-…
GSM8697166 MED15 T603D MCF7, TGFβ-0h, RNA-seq, rep2 MED15 T603D MCF7, TGFβ-…
GSM8697167 MED15 T603D MCF7, TGFβ-0h, RNA-seq, rep3 MED15 T603D MCF7, TGFβ-…
GSM8697168 WT C57 mouse hippocamous tissue, RNA-seq, rep1 WT C57 mouse hippocamou…
GSM8697169 WT C57 mouse hippocamous tissue, RNA-seq, rep2 WT C57 mouse hippocamou…
GSM8697170 WT C57 mouse hippocamous tissue, RNA-seq, rep3 WT C57 mouse hippocamou…
GSM8697171 MED15 T604A C57 mouse hippocamous tissue, RNA-seq, rep1 MED15 T604A C57 mouse h…
GSM8697172 MED15 T604A C57 mouse hippocamous tissue, RNA-seq, rep2 MED15 T604A C57 mouse h…
GSM8697173 MED15 T604A C57 mouse hippocamous tissue, RNA-seq, rep3 MED15 T604A C57 mouse h…

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