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DNA methylation profiling allows for characterization of atrial and ventricular cardiac tissues and hiPSC-CMs

Kirstin Hoff1,2, Marta Lemme2,3, Anne-Karin Kahlert1,2,4

  • 1Department of Congenital Heart Disease and Pediatric Cardiology, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Clinical Epigenetics
|June 13, 2019
PubMed

Insights

Researchers identified 16 specific DNA methylation sites to accurately distinguish between atrial and ventricular heart tissues and their derived cell types. This DNA methylation profiling offers a rapid method for characterizing cardiomyocytes in cardiovascular research and therapy.

Area of Science:

  • Cardiovascular Biology
  • Epigenetics
  • Stem Cell Biology

Background:

  • Accurate cardiac cell type differentiation is crucial for cardiac disease modeling using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).
  • Current methods for discriminating cardiac cell types are often time-consuming, expensive, and lack precision.
  • DNA methylation is a key epigenetic mechanism involved in early heart development and cardiac cell specification.

Purpose of the Study:

  • To investigate DNA methylation patterns in different cardiac tissues.
  • To identify specific CpG loci for characterizing cardiac cell types, including hiPSC-CM subtypes.
  • To develop a rapid and reliable method for phenotypic evaluation of cardiomyocytes.

Main Methods:

  • Genome-wide DNA methylation analysis using Illumina Infinium HumanMethylation450 BeadChips on atrial and ventricular human heart tissues (n=49).
  • Validation of atrial-ventricular DNA methylation patterns in an independent cohort using bisulfite pyrosequencing.
  • Identification and application of a subset of differentially methylated CpG loci for cardiac tissue and hiPSC-CM characterization.

Main Results:

  • Identification of 168 differentially methylated CpG loci between atrial and ventricular human heart tissues.
  • Definition of a subset of 16 CpG loci enabling precise characterization of atrial and ventricular cardiac tissues.
  • Successful application of these 16 CpG loci for consistent detection of cellular identity in hiPSC-CM subtypes.

Conclusions:

  • Testing DNA methylation at a small set of defined CpG sites can reliably distinguish atrial and ventricular cardiac tissues and hiPSC-CM subtypes.
  • This DNA methylation profiling method provides a rapid and reliable system for phenotypic characterization of in vitro-generated cardiomyocytes.
  • The findings open new opportunities for advancing cardiovascular research and developing patient-specific therapies.
Abstract

Keywords:
450K arrayBisulfite pyrosequencingCardiac tissue-specific DNA methylationDNA methylationEngineered heart tissue (EHT)Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM)

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