Telomerase and Oxidative Stress in Embryonic Stem Cells

Abstract

Embryonic stem (ES) cells are derivatives of the inner cell mass from pre-implantation blastocysts of early mammalian embryos. They are uncommitted and pluripotent cells with a characteristic high self renewal potential. If propagated under appropriate tissue culture conditions they can proliferate indefinitely while maintaining a high genomic stability and are in fact immortal. An important contributor to these properties is a high amount of telomerase activity. This occurs mainly via the telomere maintenance function of telomerase. However, recently it has also been shown that telomerase can localise to mitochondria and decrease intracellular oxidative stress. The final goal for the use of human embryonic stem cells (ESC) is to generate differentiated cells and products for cell replacement therapies. For this purpose, embryonic stem cells can be induced to differentiate into cells from all three germ layers: mesoderm, entoderm and ectoderm and eventually give rise to all somatic cell type of the human body. In vitro, this requires specialised growth conditions and factors which are often defined empirically rather than due to scientific evidence. For example, it emerges recently that growing ES cells under low, physiological oxygen conditions rather than atmospheric oxygen (21%) are greatly beneficial for the properties and application of these cells. This chapter will summarise our current knowledge on telomerase expression and oxygen conditions and their involvement in the maintenance of self-renewal, pluripotency and stem cell differentiation.