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Updated: Jun 25, 2025
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Single Cell Transcriptional Profiling of Adult Mouse Cardiomyocytes
Published on: December 28, 2011
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Personalized transcriptome signatures in a cardiomyopathy stem cell biobank
Emma Monte1, Takaaki Furihata1, Guangwen Wang1
1Department of Genetics, Stanford University School of Medicine.
Biorxiv : the Preprint Server for Biology
|May 27, 2024
Summary
Genetic background influences cardiomyopathy by altering gene expression, as shown in a new stem cell biobank. This study highlights ADCY5
Area of Science:
- Cardiovascular Genetics
- Stem Cell Biology
- Molecular Cardiology
Background:
- Pathogenic mutations alone do not fully explain hypertrophic (HCM) and dilated (DCM) cardiomyopathy.
- Investigating genetic background's influence on cardiomyopathy through gene expression signatures.
- Established a cardiomyopathy biobank for personalized genotype-phenotype relationship studies in human cell lines.
Approach:
- Created a stem cell biobank from 308 patients and controls, generating induced pluripotent stem cells (iPSCs) from 300 donors.
- Performed whole genome sequencing and RNA-sequencing on iPSC-derived cardiomyocytes.
- Inferred personalized co-expression networks and analyzed mutation burden and drug treatment effects.
Key Points:
- Identified 78 pathogenic mutations in iPSC lines from cardiomyopathy patients.
- DCM lines without known mutations showed increased mutation burden correlating with reduced ejection fraction.
- Discovered two distinct transcriptomic subtypes in HCM, with one showing disease severity-correlated network activation.
- Both HCM and DCM networks highlighted ADCY5 as a key hubnode, responsive to drug treatment.
Conclusions:
- Established a valuable stem cell biobank for cardiomyopathy research.
- Genetic background significantly influences pathological gene expression in cardiomyopathy.
- ADCY5 plays a crucial role in the molecular mechanisms of cardiomyopathy.
