Molecular switch matures stem cell-derived cardiomyocytes
Study provides insight into the maturation of human heart cells and potential for clinical applications
Researchers have discovered an essential molecular switch involved in the growth and maturation of embryonic heart cells.
In this study, led by Kavitha T Kuupusamy from the University of Washington (WA, USA), transcriptome analysis of RNA (focusing on miRNA in particular) produced in 20-day-old human embryonic stem cell-derived cardiomyocytes was performed and compared with more mature, 13-month old versions of these cells.
“When we compared microRNA levels seen in the 20-day-old cardiomyocytes and the more mature 13-month-old cardiomyocytes, one microRNA family, called let-7, stood out,” explained Kuppusamy. “Other miRNAs were being expressed in high levels in the more mature cells, but let-7 had increased 1000-fold. Interestingly, the let-7 family of micro RNA affects several key genes that regulate glucose metabolism, called the PI3/AKT/insulin pathway.”
To further investigate the role of let-7 miRNA in cardiac maturation, the group studied the effects of increasing and decreasing let-7 levels on stem cell-derived heart cells. It was observed that decreasing let-7 levels caused cells to revert to a glucose-based metabolism, becoming smaller, weaker and less mature both structurally and functionally. In contrast, increasing let-7 levels led to cells switching to a fatty acid-based metabolism, becoming larger, stronger and more mature. The team went on to suggest that let-7 miRNA appears to drive these changes through action on other key gene regulators.
Overall, this study indicates that let-7 miRNAs are necessary and sufficient to drive stem cell-derived cardiomyocyte maturation and the authors express hope that it may soon be possible to mature such cells in vitro through the addition of a cocktail of miRNAs to the cell culture.
- Written by Hannah Wilson
Sources: Kuppusamy KT, Jones DC, Sperber H, et al. Let-7 family of microRNA is required for maturation and adult-like metabolism in stem cell-derived cardiomyocytes. PNAS doi:10.1073/pnas.1424042112 (2015) (Epub ahead of print); University of Washington Press Release http://hsnewsbeat.washington.edu/story/key-driver-heart-stem-cell-maturation-identified