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Sustained Mesenchymal Reprogramming of Endothelial Cells after Completion of Chemotherapy [RNA-seq]

GSE300789 Homo sapiens (human) RNA-seq (gene expression) 14 samples Submitted 2025/06/26 Platform GPL18460Platform GPL34281Platform GPL24676
At a glance

RNA-seq (gene expression) · human · 14 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
Homo sapiens (human)
Samples
14 samples: 3 × HUVEC, Dox washout protocol, control vs 3 × HUVEC, Dox washout protocol, Dox vs 2 × HUVEC, Dox treatment protocol, control vs 2 × HUVEC, Dox treatment protocol, DoxGroups 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
Sustained mesenchymal reprogramming of endothelial cells after completion of chemotherapyCardio-oncology (London, England) · 2025
Summary (written by the submitters)
Cardiovascular disease is the prevailing cause of death among cancer survivors. Remarkable increase in cardiac disease burden in this group is likely due to the effects of cancer itself and, especially, cardiotoxic cancer treatments. Of the cardiotoxic cancer treatments, anthracyclines are notoriously known for causing vascular damage and severe cardiovascular complications.
Read the full summary ↓
A defining feature of cardiac damage by doxorubicin (Dox), a prototypical anthracycline, is that it typically progresses after completion of chemotherapy. As the nature of delayed deterioration is not understood we focused in this study on the events that occur upon completion of chemotherapy. We adopted the Dox treatment/washout model to examine its lasting effects on endothelial cells. Our ChIP sequencing, transcriptomic, reporter plasmid, and Smad2/3 phosphorylation experiments demonstrated the enhanced activity of the canonical TGF-b/activin pathway during Dox washout. Another notable feature was sustained mesenchymal reprogramming with significant upregulation of transcripts characteristic of fibroblastic and smooth muscle lineages. We utilized a selective ALK4/5/7 receptor kinase inhibitor, SB431542 (SB), to probe the role of the canonical TGF-/activin pathways in endothelial-to-mesenchymal reprogramming by Dox. When present during Dox washout, SB blocked increased expression of both mesenchymal transcripts and protein markers, and prevented cytoskeletal changes and fibronectin production by the treated endothelial cells. Cytoskeletal rearrangements led to increased endothelial monolayer permeability that was abolished by SB treatment. Thus, increased production of ALK4/5 receptor ligands, TGF-2 and activin, and heightened Smad2/3 activation response to these ligands during Dox washout leads to sustained mesenchymal reprogramming of endothelial cells and compromised endothelial barrier function.
Published in
Sustained mesenchymal reprogramming of endothelial cells after completion of chemotherapy
Sjostrom K, Tao S, Cobb MS et al. · Cardio-oncology (London, England) 2025 · PMID 41466436 · doi:10.1186/s40959-025-00413-7
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 GSE300789_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 PRJNA1282118 and SRA study SRP594692. Searching any of these in the dataset finder brings you back here.

Study design
3 × HUVEC, Dox washout protocol, control vs 3 × HUVEC, Dox washout protocol, Dox vs 2 × HUVEC, Dox treatment protocol, control vs 2 × HUVEC, Dox treatment protocol, Dox

Supports a between-group comparison across 10 samples.

How we read this: 4 replicated groups read from 14 sample titles; they account for 10 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
Datasets on a similar topic

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