**1. Introduction**

### **1.1 Stemness**

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The fertilized egg, also known as the zygote, is a cell of total potential and plasticity and gives rise to the embryo and extra-embryonic tissues, and ultimately the whole adult organism. This property has since been termed *totipotency*, although the transition from fertilized egg to differentiated cells of the adult tissues (somatic cells) is not direct, progressing instead through lineages of successively more differentiated and committed intermediates towards the final cell type. Thus, the zygote gives rise to the trophoblast cells and inner cell mass (ICM) of the blastocyst stage embryo, the ICM gives rise to the primordial cells committed to the ectodermal, mesodermal and endodermal lineages. To give an example lineage, the ectoderm cells give rise to the neural crest stem cells, then neural stem cells, oligodendrocyte precursors, and finally oligodendrocytes which myelinate and form the white matter of the central nervous system. Each step is more specialized and less plastic than the base or 'stem' of the branch before it. Unlike the totipotent zygote, these 'stem cells' retain the ability to self-renew in addition to their plasticity. In addition to giving rise to somatic tissues during embryogenesis, the biological role of stem cells in an adult organism is to regenerate tissues lost to injury, disease or age.

### **1.2 History**

The first stem cells discovered were the originator cells of teratomas, a rare tumor that comprised of multiple tissue types and was associated with embryonal carcinoma (EC). These EC stem cells have the then-unusual ability to self-renew indefinitely, as well as give rise to tissues from each of the three germinal layers (Kleinsmith and Pierce, 1964), a property termed *pluripotency.* Since then, many more stem cell types of varying potency have been discovered, including two more pluripotent cell types: the embryonic stem cell (ESC) is a non-cancerous analogue of the EC stem cell which is derived instead from the ICM of blastocyst stage embryos (Evans and Kaufman, 1981), and most recently induced pluripotent stem cells (iPSCs) which are produced from somatic cells that have been reprogrammed to a pluripotent state (Takahashi and Yamanaka, 2006). Pluripotent cells have since been demonstrated to have enormous potential for regenerative medicine, disease research and genetic engineering.
