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An Approach to Study Shape-Dependent Transcriptomics at a Single Cell Level
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Cell shape determines gene expression: cardiomyocyte morphotypic transcriptomes.

Payam Haftbaradaran Esfahani1, Zaher ElBeck1, Sven Sagasser1,2

  • 1Department of Medicine, Integrated Cardio Metabolic Centre (ICMC), Heart and Vascular Theme, Karolinska Institutet, 141 57, Huddinge, Sweden.

Basic Research in Cardiology
|December 25, 2019
PubMed
Summary
This summary is machine-generated.

Cardiomyocyte shape changes impact gene expression, affecting pathways crucial for heart function. Altered cell shapes, particularly pathological ones, can lead to gene downregulation and increased apoptosis, impacting cardiovascular health.

Keywords:
Cell shapeGene expression and regulationMyocardial biologySingle-cell RNA sequencing

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Area of Science:

  • Cardiology
  • Molecular Biology
  • Cell Biology

Background:

  • Cardiomyocytes change shape due to hemodynamic stress or genetic mutations.
  • These shape changes affect cellular architecture and sarcomere addition.
  • The impact of cell shape alone on cardiomyocyte gene expression remains unclear.

Purpose of the Study:

  • To investigate whether altered cardiomyocyte cell shape influences gene expression independently.
  • To characterize the transcriptomic profiles of cardiomyocytes with defined geometrical morphotypes.

Main Methods:

  • Developed a single-cell morphotyping strategy.
  • Employed single-cell RNA sequencing to analyze gene expression.
  • Correlated cardiomyocyte geometry with transcriptomic data.

Main Results:

  • Deviations from normal cardiomyocyte shapes led to significant gene expression downregulation.
  • Specific pathways, including oxidative phosphorylation and beta-adrenergic signaling, were deactivated.
  • Genes associated with cardiomyocyte apoptosis and necrosis were upregulated in pathological shapes.
  • Mechano-sensory pathways (integrin, Src kinase) were implicated in shape-dependent gene regulation.

Conclusions:

  • Cardiomyocyte shape per se significantly regulates the cardiac myocyte transcriptome.
  • Shape-dependent gene expression changes have potential implications for cardiovascular disease pathogenesis.