2019 Year 12 IB Extended Essays

expression in heart cells, however, since it is said to be involved in general cell proliferation and differentiation. Gata4, on the other hand, is equally highly specific, while also involved in heart development of an embryo, which places it as an excellent candidate, however, it is also worth noting that mutations in the gene can lead to various heart malformation and diseases. The factors Isl1 and Pitx2c are both eliminated from being considered as candidate factors as they are both not only not specifically expressed in the target cell type (as seen in graph 1, both exceeding 13 other cell types expressing similar values), but research also shows that Isl1 is involved in the regulation of insulin expression and Pitx2c is mainly involved in the development of the eye, tooth and abdominal organs, further showing the low specificity to the heart. Hand2, Hopx and Mesp1 have all shown low expression levels in the heart, however, they are also heavily involved in the formation of the heart in developing embryos. Hopx is said to be involved in certain cardiac gene expressions, however, due to its low expression levels, it is not sufficient to become a candidate factor. Both Hand2 and Mesp1 are involved in the development of the cardiac mesoderm and the heart chambers, which are largely occupied by heart epithelial and smooth muscle cells, not the target cardiomyocytes. Nkx2.5 and Smyd1 are both highly expressed in the heart. Only two other tissues express similar levels of Smyd1– skeletal muscle, which contracts to aid in movement, and the jejunum, which contracts to move food along the digestive tract. Both have certain level similarity to cardiomyocytes. Studies have also shown that the targeted deletion of this gene prevented the maturation of cardiomyocytes (Gottlieb, et al., 2002), making this an important transcription factor in the tissue type and therefore, is considered a candidate for the selection. Nkx2.5 is especially exclusive to the heart and that no other tissue type expresses a similar level of this gene, implying the importance of this gene to the heart. However, this gene does not contribute to the differentiation of cardiomyocytes, rather, it contributes largely to the development of the atrial, ventricular septation and AV valve formation. Therefore Nkx2.5 will not be considered a candidate factor. Tbx5, Myocd and Hrt2 are three transcription factors that have a medium expression level in the heart but vary largely in functions. Myocd is said to be involved in epithelial cell dense areas such as the heart chambers and the aorta, it is mainly involved in the differentiation of smooth muscle cell lineage. Both hrt2 and Tbx5 are cardiac specific, however, due to its medium level of expression, other factors with higher specificity will be sufficient in transforming the cell, therefore all three of the genes will not be considered candidate factors. Mef2c plays a role in maintaining the differentiated state of muscle cells and therefore it is highly relevant to the target cell type despite the low level of expression in the heart. This transcription factor will likely give cardiomyocytes the ability to contract and function like muscle cells, therefore will be considered as an appropriate candidate factor to the selected. According to the research results, Gata4 is an excellent candidate as it is highly specific to the heart with only four other tissue types expressing it. It is also heavily involved in myocardial differentiation and function, therefore, Gata4 will be one important transcription factor to be selected for the cell reprogramming process. Although cardiac septal defects and cancers have been associated with the gene encoded by Gata4, it does not mean that making the starting cell produce Gata4 will cause the same diseases.

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