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Proteomic Analysis Reveals Temporal Changes in Protein Expression in Human Induced Pluripotent Stem Cell-Derived

Nicola Hellen1, Carolina Pinto Ricardo1, Karine Vauchez1

  • 11 Myocardial Function, National Heart and Lung Institute, Imperial College, London, United Kingdom.

Stem Cells and Development
|February 14, 2019
PubMed

Insights

Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) show temporal protein expression changes during 30-day culture. Early changes involve protein synthesis reduction, followed by metabolic pathway shifts, indicating hiPSC-CM development.

Area of Science:

  • Cardiovascular Biology
  • Stem Cell Biology
  • Proteomics

Background:

  • Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are promising for regenerative medicine and drug screening.
  • hiPSC-CMs exhibit key cardiomyocyte features but resemble fetal/neonatal cells, necessitating further characterization.
  • Understanding temporal protein expression changes is crucial for optimizing hiPSC-CM applications.

Purpose of the Study:

  • To investigate the effects of short-term (30-day) in vitro culture on hiPSC-CM protein expression.
  • To identify temporal changes in protein profiles related to cardiomyocyte function and maturation.
  • To assess the developmental trajectory of hiPSC-CMs during early culture.

Main Methods:

  • Utilized tandem mass tags for cell lysate labeling and multiplexing.
  • Analyzed global protein expression changes over a 30-day culture period post-thaw.
  • Quantified time-dependent alterations in proteins associated with cardiomyocyte function.

Main Results:

  • Pronounced protein expression changes occurred within the first 2 weeks, marked by reduced proteins in synthesis and ubiquitination.
  • Between weeks 2 and 4, metabolic pathways dominated, suggesting a shift from glycolysis to oxidative phosphorylation.
  • Detected time-dependent changes in proteins related to contraction, excitation-contraction coupling, and metabolism, with varied functional outcomes.

Conclusions:

  • hiPSC-CMs undergo significant temporal protein expression changes during 30 days of in vitro culture.
  • These changes indicate a developmental progression, including metabolic shifts, though not always leading to anticipated maturation.
  • The study provides insights into hiPSC-CM development, essential for their effective use in research and therapy.

Keywords:
cardiomyocytepluripotentproteomics

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