WE PROPOSE TO INVESTIGATE THE EFFECT OF GRAVITY ON FUNDAMENTAL PROPERTIES OF MAMMALIAN STEM CELLS DURING DIFFERENTIATION OF 3-D CULTURES OF INDUCED PLURIPOTENT STEM (IPS) CELLS. EXPERIMENTS ABOARD THE ISS STS AND GROUND-BASED SIMULATIONS HAVE DEMONSTRATED THAT MICROGRAVITY INFLUENCES GENE EXPRESSION CELL PROLIFERATION AND DIFFERENTIATION IN STEM CELLS. HOWEVER THE MECHANISM BEHIND THESE OBSERVATIONS IS NOT CLEARLY UNDERSTOOD. IN THIS STUDY WE WILL INVESTIGATE HOW EXPOSURE TO MICROGRAVITY FUNDAMENTALLY ALTERS THE REGULATION OF OCT4 A TRANSCRIPTION FACTOR NECESSARY TO MAINTAIN PLURIPOTENCY AND HOW THESE CHANGES CAN AFFECT THE TIMING PROGRESSION AND OUTCOMES OF CELL DIFFERENTIATION. OUR LABORATORY HAS CREATED AN OCT4:CREER MTMG TRANSGENIC MOUSE THAT FOR THE FIRST TIME ALLOWS LINEAGE TRACING OF OCT4 EXPRESSION IN STEM CELLS AND THEIR PROGENY. WE WILL USE IPS CELLS DERIVED FROM THIS MODEL TO DETERMINE THE INFLUENCE OF MICROGRAVITY ON THE LOSS OF PLURIPOTENCY AND DIFFERENTIATION.