Growing up we have all heard the phrase, “You are what you eat.” Just like our bodies, stem cells require large quantities of fuel for energy and growth. The same is true for heart cells that continually drive blood flow. Therefore, understanding how stem cells and cardiac cells they generate consume and use different foods is important for characterizing their clinical potential. This grant aims to study how different nutritional fuels influence stem cell and cardiomyocyte (heart cell) growth, differentiation, and function. Using advanced methods that allow us to track how sugar (carbs), protein, and fat are consumed and produced by stem cells, we have identified key nutritional factors that affect stem cell performance and function. Surprisingly, most advanced stem cell media are lacking in several important factors. This deficiency negatively impacts stem cell metabolism in a number of ways, causing increased nutrient consumption, decreased respiration, and oxidative stress. Using this information we have developed improved stem cell growth conditions that mitigates these effects. Finally, we have compared the metabolism of stem cell-derived heart cells to parental stem cells, identifying key differences that will serve as benchmarks to functionally validate the performance and “maturity” of cardiac cells.