Patient-derived heart cells points to genetic control of cardiac function, US study finds
Instances of cardiac function/malfunction, such as irregular rhythms or heart failure, has been unclear in genome studies to date but researchers at the University of California San Diego (UCSD) School of Medicine have discovered that genetic variations influence heart function through the binding of a protein – essentially, turning “on/off” genes involved in heart development.
After obtaining skin samples from seven people from three generations of a single family, the researchers converted the cells into induced pluripotent stem cells (iPSCs). As iPSCs can replicate and also differentiate into a specialised cell types, they were directed into becoming heart cells that actually “beat” in the laboratory dish.
The genetic/molecular variation of these cells affected the protein NKX2-5, a transcription factor that must bind to non-coding regions of the genome.
Kelly A. Frazer, the Director of the Institute for Genomic Medicine at UCSD, explains, “NKX2-5 binds to many different places in the genome near heart genes, so it makes sense that variation in the factor itself or the DNA to which it binds would affect that function, so multiple heart-related traits can share a common mechanism – in this case, differential binding of NKX2-5 due to DNA variants.”
Since related individuals tend to share similar genetic variants, Frazer’s team was able to validate their findings by analysing the same variants in multiple samples. However, Frazer thinks there could be more genetic variants in the genome involved with NKX2 and other important cardiac transcription factors across the entire population.
Meanwhile, the team plans to further investigate cardiovascular genetics and other organ systems using this method.
“We are now expanding this same model system to look at many different transcription factors, across different tissue types, such as pancreas and retina epithelia, and scaling it up to include more families,” according to Paola Benaglio, a postdoctoral researcher in Frazer’s lab.
