How can you mend a broken heart? Well if researchers at Stanford University are right, then one day all you’ll need are some stem cells and miR-499 to cure a bad case of heartache (well, at least the kind that follows a heart attack. The bad breakup kind will still be up to relationship experts and self-help gurus to solve.)
Of course, it’s not exactly that simple. Human embryonic stem cells (hESCs) may one day be used to help regenerate damaged heart tissue post-infarction, but before that can happen there is still much to learn about turning hESCs into full-fledged cardiomyocyte cells, and how miRNAs are involved. So, to learn more about how they tick the Stanford scientists decided to study the miRNA profiles of stem cell derived cardiomyocytes (hESC-CMs).
The first step was to look at FACS sorted hESC-CMs on miRNA micorarrays to find which miRNAs were being expressed. The team found many of the usual heart miRNA suspects like miR-1, miR-133 and miR-208, but they also found a novel one, miR-499, that caught their attention.
The team next used miRNA over-expression and knockdown reagents to explore miR-499’s role in cardiomyocyte development and compared the results to the better known miR-1 and miR-208. They discovered that miR-499 shared many of the same targets as the heart specific miR-208, and found that miR-499 expression led to upregulation of myosin heavy-chain genes, and MEF2C, a cardiac transcription factor, as well.
So it looks like miR-499 is definitely a player in cardiomyocyte differentiation… and maybe someday it’ll even help fix broken hearts.
Read all of the heartwarming details in Circulation: Cardiovascular Genetics, October 2010
Learn more about the Lenti-miR miRNA precursors and miRZip anti-miRNA constructs used in this paper at the System Biosciences website.