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Multiscale profiling of tyrosine kinase inhibitor cardiotoxicity reveals mechanosensitive ion channel PIEZO1 as cardioprotective [bulk RNA-seq]

GSE309795 Homo sapiens (human) Single-nucleus RNA-seq 72 samples Submitted 2025/11/19 Platform GPL24676
At a glance

Single-nucleus RNA-seq · human · 72 samples

What it is
Single-nucleus RNA-seqGene activity measured in individual nuclei (used when whole cells are hard to isolate, for example from frozen tissue). Read from the summary: GEO's own type field only says 'expression profiling by sequencing', so confirm it in the paper.
Organism
Homo sapiens (human)
Samples
72 samples: 19 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
Multiscale profiling of tyrosine kinase inhibitor cardiotoxicity reveals mechanosensitive ion channel PIEZO1 as cardioprotectiveScience translational medicine · 2025
Summary (written by the submitters)
Tyrosine kinase inhibitors (TKIs) have improved cancer outcomes but are limited by cardiovascular toxicity, most notably hypertension and heart failure. The underlying mechanisms remain poorly understood, hindering the development of protective strategies. Here, we investigated the role of endothelial mechanotransduction in mediating vascular and cardiac injury caused by the VEGFR-targeting TKI sunitinib.
Read the full summary ↓
Using patient-specific induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) and a mouse model of TKI-induced hypertension, we identified downregulation of PIEZO1, a mechanically activated ion channel, as a central driver of endothelial dysfunction. Restoring PIEZO1 expression, either pharmacologically with Yoda1, a selective agonist, or through inducible overexpression in iPSC-ECs, reversed sunitinib-induced endothelial dysfunction and mitigated its hypertensive effects, providing both mechanistic and genetic validation of PIEZO1’s protective role against vascular toxicity. In mice, Yoda1 co-treatment prevented the long-term cardiac dysfunction observed following sunitinib exposure, and normalized elevations in circulating cardiac stress biomarkers. Single-nuclei multiomic profiling of mouse hearts revealed that sunitinib exposure activated chromatin remodeling and fibrogenic programs, which were reversed with PIEZO1 activation. Human engineered cardiac organoids further demonstrated that sunitinib impaired cardiomyocyte function only in the presence of endothelial cells, confirming a role for disrupted endothelial-cardiomyocyte crosstalk in TKI cardiotoxicity. Together, these findings identify endothelial PIEZO1 as a critical mediator of TKI-induced hypertension and cardiac dysfunction and highlight PIEZO1 activation as a potential therapeutic strategy for protecting cardiovascular health during cancer therapy.
Published in
Multiscale profiling of tyrosine kinase inhibitor cardiotoxicity reveals mechanosensitive ion channel PIEZO1 as cardioprotective
Manhas A, Liu Y, Noishiki C et al. · Science translational medicine 2025 · PMID 41406242 · doi:10.1126/scitranslmed.adv9403
This dataset
Open GSE309795 in finder → Find more human 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 GSE309795_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: Single-cell studies usually ship their counts as 10x files (matrix.mtx, barcodes.tsv, features.tsv), an .h5 file, or an .rds / .h5ad object that Seurat or Scanpy can open. Look for those among the supplementary files.

Also filed as BioProject PRJNA1363194 and SRA study SRP644576. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 41406242) ↗
Study design
19 conditions, mostly in triplicate
iPSC_EC_Sunitinib ×12 iPSC_EC_Control ×12 iPSC_EC_Yoda1 ×6 iPSC_EC_Tet-on_Basal ×3 iPSC_EC_Tet-on_Doxy ×3 iPSC_EC_Tet-on_Sun ×3 HAo_EC_Control ×3 HAo_EC_Sunitinib ×3 +11 more

Supports a between-group comparison across 72 samples.

How we read this: 19 replicated groups read from 72 sample titles; they account for 72 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

+ 32 more — browse all 72 samples with per-sample file links →

Datasets on a similar topic

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