![]() ![]() The first stream was initialized when Gurdon produced tadpoles from an unfertilized egg using a nucleus from frog intestinal cell in 1962. Merger of three scientific research streams that facilitates the development of iPSCs. ![]() This major breakthrough was the demonstration that ectopic expression of cellular transcription factors by retroviral vector transduction in mouse fibroblasts was sufficient to reverse a somatic cell into a pluripotent-like state ( Fig. 2) has led to the landmark discovery in stem cell research. The depth of Yamanaka's perception through the discoveries in somatic cell nuclear transfer, 10 cellular fusion, 11 ESC research, 1, 12 and understanding of pluripotency related transcription factors 13, 14 ( Fig. In addition, the potential applications of iPSCs in cell replacement therapy and the synergy of iPSCs and clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 gene editing tool in therapeutics research are also reviewed. This review discusses the scientific framework that led to the reprogramming of induced pluripotent stem cells (iPSCs), the roles of the OSKM in reprogramming the mature differentiated cells into iPSCs, and the benefits and drawbacks of the reprogramming strategies. Takahashi and Yamanaka 9 were the first to demonstrate that the pluripotent stem cells could be induced from the adult fibroblasts by introducing four transcription factors, octamer-binding transcription factor 3/4 (Oct3/4), SRY (sex determining region Y)-box 2 (Sox2), Krüppel-like factor 4 (Klf4), and cellular-Myelocytomatosis (c-Myc) (OSKM). 8 Extensive research has been conducted in identifying these factors. It was hypothesized that the factors that play important roles in the maintenance of ESC identity also play pivotal roles in the induction of pluripotency in the somatic cells. However, little is known about this process. The conservation of genome during development serves as a basis of principle for nuclear reprogramming. ![]() The transplanted genome is reprogrammed into a pluripotent state, whereby the egg undergoes cell division and a cloned animal is produced. The nucleus of a differentiated cell is transplanted into an enucleated egg in meiotic metaphase by nuclear transfer. 6 These momentous findings concluded that differentiated cells still retain the genetic memory that is important for an organism's development and that oocytes contain factors that can reprogram the mature cell's nuclei. 4, 5 More than 30 years later, Dolly the sheep was cloned from an adult somatic cell using nuclear transfer technology. Gurdon entirely altered this paradigm by producing a fully functional tadpole from an unfertilized egg containing a nucleus from a differentiated intestinal epithelium cell of a mature frog ( Fig. It was initially thought that the genome of a mature cell is everlastingly locked in a somatic state and unable to revert into a fully ESC-like state. The ethical and legislative debates revolving around the use of human embryo in research have been circumvented by the advancements in nuclear reprogramming. 2 However, human ESC-related research is ethically controversial because it involves the destruction of human embryo. 1 ESCs offer tremendous potential applications in biomedical research and regenerative medicine, opening new avenues for therapeutic strategies aimed at cell replacement in degenerative, traumatic, and ischemic disorders. These cells are pluripotent, that is, they have an indefinite ability to self-renew while maintaining the potential to differentiate into all cell types. Human embryonic stem cells (ESCs) are derived from the inner cell mass of a developing embryo at the blastocyst stage. ![]()
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