Molecular Medicine Israel

UCLA Stem Cell Researchers Uncover Mechanism that Regulates Human Pluripotent Stem Cell Metabolism

The EMBO Journal, 2011; DOI: 10.1038/emboj.2011.401
Jin Zhang, Ivan Khvorostov, Jason S Hong, Yavuz Oktay, Laurent Vergnes, Esther Nuebel, Paulin N Wahjudi, Kiyoko Setoguchi, Geng Wang, Anna Do, Hea-Jin Jung, J Michael McCaffery, Irwin J Kurland, Karen Reue, Wai-Nang P Lee, Carla M Koehler and Michael A Teitell.
UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells”.


Human pluripotent stem cells, which can develop into any cell type in the body, rely heavily on glycolysis, or sugar fermentation, to drive their metabolic activities.

In contrast, mature cells in children and adults depend more on cell mitochondria to convert sugar and oxygen into carbon dioxide and water during a high energy-producing process called oxidative phosphorylation for their metabolic needs.

How cells progress from one form of energy production to another during development is unknown, although a finding by UCLA stem cell researchers provides new insight for this transition that may have implications for using these cells for therapies in the clinic.

Based mostly on visual appearance, it had been assumed that pluripotent stem cells contained undeveloped and inactive mitochondria, which are the energy-producing power plants that drive most cell functions. It was thought that stem cell mitochondria could not respire, or convert sugar and oxygen into carbon dioxide and water with the production of energy. This led most scientists to expect that mitochondria matured and gained the ability to respire during the transition from pluripotent stem cells into differentiated body cells over time.

Surprisingly, UCLA stem cell researchers discovered that pluripotent stem cell mitochondria respire at roughly the same level as differentiated body cells, although they produced very little energy, thereby uncoupling the consumption of sugar and oxygen from energy generation. Rather than finding that mitochondria matured with cell differentiation, as was anticipated, the researchers uncovered a mechanism by which the stem cells converted from glucose fermentation to oxygen-dependent respiration to achieve full differentiation potential.

The four-year study appears in the Nov. 15, 2011 issue of The EMBO Journal, a peer-reviewed journal of the European Molecular Biology Organization. Teitell collaborated with Carla Koehler, a UCLA professor of chemistry and biochemistry, for the study.

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