Molecular switch matures stem cell-derived cardiomyocytes

Study provides insight into the maturation of human heart cells and potential for clinical applications

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May 21, 2015
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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

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