2019 Year 12 IB Extended Essays

1 Introduction

Masaki Ieda; Ji-DongFu, et al completed a study in 2010 and successfully transformed postnatal cardiac or dermal fibroblasts into cardiomyocytes by introducing a combination of 3 transcription factors (Ieda, et al., 2010). Researchers from this study selected 14 of the early cardiac factors as the starting material (Baf60c, Gata4, Hand2, Hopx, Hrt2, Isl1, Mef2c, Mesp1, Myacd, Nkx2.5, Pitx2c, Smyd1, Srf, Tbx5), and by developing ‘an assay system in which the induction of mature cardiomyocytes from fibroblasts could be analysed quantitatively by reporter-based fluorescence-activated cell sorting (FACS)’, they narrowed down to the three most significant transcription factors involved in the transformation process. At the conclusion of the study, the researchers stated that ‘Further studies in human cells and advances in safe delivery of defined factors will be necessary to advance this technology for potential regenerative therapies.’ (Ieda, et al., 2010) This investigation will utilise a method different from that of this study, and will attempt to validate the feasibility of the end three transcription factors that were selected in this study. 1.1 Cell division and transcription factors The nucleus in each cell of the human body stores the entire human genome, which contains around 20,000 to 25,000 genes, however, gene expression is regulated via a process known as gene regulation (VanSomeren, 2017). In each healthy cell, depending on its location and function, only expresses a fraction of its genes, the rest is being tightly wrapped in to chromosomes in the nucleus and repressed. During the expression of genes, the DNA is converted to the RNA, which is then turned into a functional protein, or in other cases, another RNA. The first step of gene expression is transcription, which is the process of the DNA producing their corresponding mRNA copy. The entire process of transcription is dependent upon specific protein factors known as transcription factors, which are activated by signals from the environment or from other cells. These transcription factors bind to particular DNA sequences in gene regulatory regions and control the transcription process by increasing or decreasing the level of transcription and thus determine the amount of final protein product made by a gene (Latchman, 1993). 1.2 Stem cells and induced pluripotent stem cells (iPSCs) Stems cells in early human embryonic development are extremely versatile and can differentiate along different pathways into any of the cell types found in human tissues (Allott & Mindorff, 2014). Even though it was thought that the differentiation of a cell is unidirectional, and that once a cell is differentiated it will not be able to turn back into a stem cell. In 2006, Japanese researchers Kazutoshi Takahashi and Shinya Yamanaka turned mouse embryonic and adult fibroblasts into induced pluripotent stem cells by artificially introducing four selected transcription factors to the cell (Kazutoshi Takahashi, 2006). This marked the turning point of stem cell research as it is thought before that the only way to

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