Year 4 (NCE 6-mo)

Mitochondria are the power of the cell, providing energy in the form of ATP and NADH for cellular activities.  In the pluripotent state, mitochondrial activity is relatively limited.  However, as a pluripotent stem cell differentiates into a determined lineage, mitochondrial energy production increases as the cell moves from a typically hypoxic to normoxic environment.  Initial studies showed that a small molecule probe that interfered with mitochondrial function selectively killed pluripotent cells but not differentiated lineages.  With the ultimate goal of developing stem cell therapies, transplanting stem cells into patients to correct a disease is a potentially important application.  However, transplanting stem cells can have a potential danger if the cells fail to differentiate into the specified lineage and instead move into an environment that could induce teratomas.  This probe was tested to determine if it could be useful for characterizing the differentiation process with the ultimate goal of making stem cell therapies safer.  Mechanistic studies were also completed to understand important aspects of mitochondrial function as the stem cell differentiates and changes environments.  Future studies to further these outcomes will focus on optimizing the probe for stem cell differentiation studies and identifying key steps in mitochondrial physiology that are important in the stem cell differentiation process.  Studies with these probes highlighted the importance of mitochondrial physiology in stem cell maintenance and differentiation pathways.