**1. Introduction**

Stem cells are a unique subset of cells that possess the biological properties of self-renewal and differentiation. The term "Stammzelle" (German for stem cell) was first used by a German biologist Ernst Haeckel in 1868 regarding unicellular organisms as the phylogenetic ancestors of multicellular organisms [1]. In 1877, Haeckel further applied the notion of stem cells to describe the fertilized egg cell as the cell of origin for all the cells in an organism [2].

Indeed, there are stem cells of different potency that not only form the foundation of any organisms but also throughout the life of the organism maintain tissue homeostasis. Following egg fertilization with a sperm, a zygote is generated (**Figure 1A**). This single-cell zygote and the cells that immediately arise in the first few divisions are totipotent stem cells, as they are capable of becoming a whole embryo including the extra-embryonic tissue, i.e., placenta. After about 5 days of human embryonic development, the zygote develops into a blastocyst. The preimplantation blastocyst consists of a mostly hollow ball of cells, with the outer cell layer as trophoblast that develops into the placenta and the inner cell mass (ICM) that is pluripotent and gives rise to all cell types in the body. These pluripotent stem

### **Figure 1.**

*Derivation of pluripotent stem cells (PSCs) including embryonic stem cells (ESCs) from fertilization of oocytes and sperm (A), nuclear transfer ESCs (NT-ESCs) from somatic cell nuclear transfer (SCNT) of somatic cell nuclei into denucleated oocytes (B), and induced pluripotent stem cells from forced expression of Yamanaka transcription factors in somatic cells (C). All the three types of PSCs can be propagated extensively in vitro and undergo directed differentiation into any cell type of the body, which can be utilized in disease modeling and drug screening and developed as cell-based therapies. As generation of ESCs involve disruption of the embryos, they can only be used as an allogenic source, while NT-ESCs and iPSCs can be developed in both allogenic and autologous settings.*

cells (PSCs) in the ICM are the source for embryonic stem (ES) cells [3]. Apart from PSCs, there are tissue-specific stem cells residing in several organs such as the skin, gut, blood, and brain, also referred to as "adult" or "somatic" stem cells with self-renewal and multipotent differentiation capacity that are responsible for most regenerative activities throughout the life of the organism.
