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Epigenetic Regulation of Cardiac Differentiation of Embryonic Stem Cells and Tissues
Published on: June 3, 2016
Genome-wide transcriptional profiling of human embryonic stem cells differentiating to cardiomyocytes
Abdelaziz Beqqali1, Jantine Kloots, Dorien Ward-van Oostwaard
1Hubrecht Laboratory, Uppsalalaan 8, 3584 CT Utrecht, The Netherlands.
Insights
Human embryonic stem cells (hESCs) can generate heart cells, aiding in cardiac repair. This study maps gene expression during hESC differentiation, revealing key developmental pathways for improved cell therapy.
Area of Science:
- Cardiology
- Stem Cell Biology
- Developmental Biology
Background:
- Mammalian hearts cannot regenerate after myocardial infarction.
- Human embryonic stem cells (hESCs) offer potential for cardiomyocyte replacement therapy.
- Understanding stem cell differentiation is key to scaling cell production for transplantation.
Purpose of the Study:
- To identify and validate gene expression patterns during hESC differentiation into cardiomyocytes.
- To enhance stepwise differentiation protocols for cardiac progenitor cells.
- To uncover novel genes involved in cardiac development and potential causes of congenital heart defects.
Main Methods:
- Genome-wide transcriptional profiling using microarray technology on hESCs undergoing cardiomyocyte differentiation.
- Validation of time-dependent gene expression patterns.
Main Results:
- Identified sequential waves of gene expression mirroring early embryonic development, including mesoderm, endoderm, cardiac progenitor, and fetal cardiomyocyte markers.
- Discovered known and novel genes associated with cardiac differentiation.
- Demonstrated a novel hESC differentiation protocol efficient for transcriptional profiling.
Conclusions:
- The identified gene expression patterns enable enhancement of stepwise differentiation protocols.
- Facilitates isolation and expansion of cardiac progenitor cells for therapeutic applications.
- Provides insights into congenital heart defect etiology through novel gene discovery.
Abstract:
Mammals are unable to regenerate their heart after major cardiomyocyte loss caused by myocardial infarction. Human embryonic stem cells (hESCs) can give rise to functional cardiomyocytes and therefore have exciting potential as a source of cells for replacement therapy. Understanding the molecular regulation of cardiomyocyte differentiation from stem cells is crucial for the stepwise enhancement and scaling of cardiomyocyte production that will be necessary for transplantation therapy. Our novel hESC differentiation protocol is now efficient enough for meaningful genome-wide transcriptional profiling by microarray technology of hESCs, differentiating toward cardiomyocytes. Here, we have identified and validated time-dependent gene expression patterns and shown a reflection of early embryonic events; induction of genes of the primary mesoderm and endodermal lineages is followed by those of cardiac progenitor cells and fetal cardiomyocytes in consecutive waves of known and novel genes. Collectively, these results permit enhancement of stepwise differentiation and facilitate isolation and expansion of cardiac progenitor cells. Furthermore, these genes may provide new clinically relevant clues for identifying causes of congenital heart defects.
