GEO series

Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy

GSE261750 Homo sapiens (human) Single-nucleus RNA-seq 2 samples Submitted 2024/09/16 Platform GPL24676

At a glance

Single-nucleus RNA-seq · human · 2 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: 2 samples
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: Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathyThe Journal of clinical investigation · 2025

Summary (written by the submitters)

Loss of Bcl2-associated anthanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). Recent studies show that BAG3 regulates sarcomere protein turnover in cardiomyocytes (CMs). However, the function of BAG3 in other cell types of the heart is unknown. In this study, we used an isogenic pair of BAG3 knockout and wild-type human induced pluripotent stem cells (hiPSC) to interrogate the function of BAG3 in hiPSC-derived cardiac fibroblasts (CFs).

Read the full summary ↓

Generating a series of conditional knockout (cKO) engineered heart tissues, we determined the contribution of CF BAG3 to engineered heart tissue function. Despite normal CM genotype, the loss of fibroblast-specific BAG3 (FBKO) caused a reduction in contractile force and an increase in cardiac fibrosis in the engineered heart tissues, recapitulating the phenotype of DCM. Using culture substrates with defined stiffness, we decoupled the mechanical activation of fibroblasts from their ligand response. In BAG3-/- CFs, we observed an increased sensitivity to transforming growth factor β (TGFβ) signaling and activation of a fibrogenic response when cultured at physiological stiffness (8kPa). Mechanistically, loss of BAG3 increased transforming growth factor receptor 2 (TGFBR2) levels. BAG3 binds TGFBR2 and mediates its ubiquitination and proteasomal degradation. To further validate these results, we performed single-nuclei sequencing of cardiac tissue from DCM patients carrying pathogenic BAG3 mutations. Mutations in BAG3 increased fibrotic gene expression in cardiac fibroblasts. Together, these results extend our understanding of the roles of BAG3 in heart disease beyond the cardiomyocyte-centric view. This study also highlights the ability of hiPSC-based models and tissue engineering to answer questions about the cell-type specific aspects of cardiac disease.

Published in

Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy

Wang BZ, Morsink MA, Kim SW et al. · The Journal of clinical investigation 2025 · PMID 39744939 · doi:10.1172/JCI181630

This dataset

Open GSE261750 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 GSE261750_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 PRJNA1088543 and SRA study SRP495530. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 39744939) ↗

Samples in this study

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+ 2 more — browse all 2 samples with per-sample file links →

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Metadata from NCBI GEO, cached and refreshed periodically — the NCBI page above is authoritative. Downloads link straight to NCBI/ENA; nothing is proxied through BioTransfer.