Cell lineage choice during differentiation of trophoblast stem cells (tsc) is dependent on oxygen levels, and mediated by stress enzyme pathways and mitochondrial function

CELL LINEAGE CHOICE DURING DIFFERENTIATION OF TROPHOBLAST STEMCELLS (TSC) IS DEPENDENT ON OXYGEN LEVELS, AND MEDIATED BY STRESSENZYME PATHWAYS AND MITOCHONDRIAL FUNCTIONbySICHANG ZHOUDecember 2011Advisor: Dr. Daniel A. RappoleeMajor: Physiology, Concentration in Reproductive SciencesDegree: Doctor of PhilosophyIn general, stress is defined as a noxious factor in a broad spectrum (chemical,biological or physical). Stress response of human body can be divided into three levels-integrate, organ/tissue or cellular response. Trophoblast stem cell (TSC) is one of theearliest differentiated stem cell within blastocyst, which is the stage of preimplantationembryo developed from fertilized egg. Different from another pluripotent embryonicstem cell, which is derived from inner cell mass in blastocyst and develop into fetus,multipotent TSC will specifically differentiate into all kinds of cell subtypes consisting ofplacenta by which nutrient and oxygen from mom as well as metabolites from fetus canbe exchanged.In our previous studies based upon preimplantation embryo and TSC, fourparameters for defining stress are identified: 1) decreased cell accumulation; 2)increased apoptosis; 3) decreased mutipotent markers and increased cell lineagemarkers; 4) increased activity of stress enzyme SAPK/JNK. By these parametersapplying on different O2 cultured TSC, we identified that 2% O2 is the optimal oxygenenvironment for TSC mutipotency maintenance and proliferation. Additionally, TSC