GEO series

Human Induced Pluripotent Stem Cells Recapitulate Breast Cancer Patients’ Predilection to Doxorubicin-Induced Cardiotoxicity

GSE76314 Homo sapiens (human) Single-cell RNA-seq 12 samples Submitted 2016/04/18 Platform GPL11154

At a glance

Single-cell RNA-seq · human · 12 samples

What it is: Single-cell RNA-seqGene activity measured in thousands of individual cells, so cell types can be told apart. 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)
Topic: Breast cancerThis series is part of our curated briefing on it.
Samples: 12 samples: 12 samples, each with a distinct title — no replicated groupsGroups 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.

Summary (written by the submitters)

Doxorubicin (Adriamycin) is an anthracycline chemotherapy agent effective in treating a wide range of malignancies1 with a well-established dose-response cardiotoxic side-effect that can lead to heart failure2-4. Even at relatively low cumulative doses of 200–250 mg/m2, the risk of cardiotoxicity is estimated at 7.8% to 8.8%4,5. Doxorubicin-induced cardiotoxicity (DIC) can range from asymptomatic reductions in left ventricular ejection fraction (LVEF) to highly symptomatic heart failure6,7.

Read the full summary ↓

At present, it is not possible to predict which patients will be affected by DIC or adequately protect patients who are at risk for suffering this devastating side-effect8. Here we demonstrate that patient-specific human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can recapitulate individual patients’ predilection to DIC at the single cell level. hiPSC-CMs derived from breast cancer patients who suffered clinical DIC are consistently more sensitive to doxorubicin toxicity, demonstrating decreased cell viability, mitochondrial/metabolic function, calcium handling, and antioxidant pathway gene expression, along with increased reactive oxygen species (ROS) production compared to hiPSC-CMs from patients who did not experience DIC. Together, our data indicate that hiPSC-CMs are a suitable platform for identifying and verifying the genetic basis and molecular mechanisms of DIC.

This dataset

Open GSE76314 in finder → Find more human RNA-seq datasets → Breast cancer landscape →

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 GSE76314_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 PRJNA306880 and SRA study SRP067762. Searching any of these in the dataset finder brings you back here.

NCBI GEO page ↗ Paper (PMID 27089514) ↗

Study design

12 samples, each with a distinct title — no replicated groups

Any grouping that defines a comparison lives in the sample characteristics, which GEO records separately from the titles.

How we read this: Read from 12 sample titles: 12 distinct titles with little repetition. 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

GSM1981189 CON1 0uM
GSM1981190 CON1 1uM
GSM1981191 CON3 0uM
GSM1981192 CON3 1uM
GSM1981193 CON4 0uM
GSM1981194 CON4 1uM
GSM1981195 CH1 0uM
GSM1981196 CH1 1uM
GSM1981197 CH3 0uM
GSM1981198 CH3 1uM
GSM1981199 CH4 0uM
GSM1981200 CH4 1uM

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GSE104675 Role for the Transcriptional Activator ZRF1 in Breast Cancer Progression and Endocrine Resistance 6 samples same disease briefing · shares breast
GSE10886 A Supervised Risk Predictor of Breast Cancer Based on Biological Subtypes 226 samples same disease briefing · shares breast
GSE10885 An integromic analysis reveals that metaplastic carcinomas are distinct from basal-like tumors. 244 samples same disease briefing
GSE79413 Human induced pluripotent stem cell–derived cardiomyocytes recapitulate the predilection of breast cancer patients to doxorubicin-induced cardiotoxicity 8 samples shares doxorubicin-induced, cardiotoxicity, recapitulate, predilection, pluripotent, induced, breast, stem
GSE88944 High-Throughput Screening of Human Induced Pluripotent Stem Cell Cardiomyocytes Predicts Tyrosine Kinase Inhibitor Cardiotoxicity 10 samples shares cardiotoxicity, pluripotent, induced, stem
GSE303402 Human induced pluripotent stem cell-derived skin organoids recapitulate donor-specific pigmentation diversity 2 samples shares recapitulate, pluripotent, induced, stem

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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.