In the past year, we examined the importance of metabolic pathways in human induced pluripotent stem cells. We first focused on an energy-gauge, the energy-sensing protein kinase called AMP-dependent protein kinase (AMPK). We found that this energy-sensing protein is expressed in human stem cells and that it gets activated upon nutrient deprivation. We were also able to model human mutations in this pathway in these stem cells. Finally, we were able to identify novel substrates of AMPK in human cells and to verify that they were indeed targeted by AMPK in human stem cells. Together, these data indicate that energy-sensing pathway are highly active in human stem cells and could be very important for the generation, quality, and differentiation of these cells into specific cell types such as cardiac cells. Another portion of our program is to develop novel methodology to analyze in an unbiased manner the metabolism of human stem cells with the goal to improve their function and ability to differentiate into cardiac or neuronal cells. In the past year, we have optimized new approaches that can detect in a very sensitive and unbiased manner different types of metabolites in cells, in particular lipid metabolites. As low energy leads to lipid utilization by cells, understanding lipid metabolism will be a key step in understanding stem cell function and quality. Together, our analysis should give insight into the metabolism of stem cells, which could improve their generation, quality, and ability to differentiate into specialized cells for regenerative medicine.