Bioinformatic analysis of the four transcription factors used to induce pluripotent stem cells

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Abstract
Induced pluripotent stem (iPS) cells are a type of pluripotent stem cell artificially derived from non-pluripotent cells by overexpressing the transcription factors Oct4, Sox2, Klf4 and Nanog. These transcription factors play a pivotal role in stem cells; however, the function of these factors are not fully characterized. In this study, we analyzed Oct4, Sox2, Klf4 and Nanog in ten different species using bioinformatics, to provide more knowledge of the function of these genes. Nanog does not exist in the invertebrates Caenorhabditis elegans and Drosophila melanogaster, indicating that the absence of Nanog may be responsible for the developmental differences between vertebrates and invertebrates. Construction of phylogenetic trees confirmed that the function of Nanog is conserved from fish to mammals. The effect of alternative splicing on the protein domains present in Oct4, Sox2, Klf4 and Nanog were also analyzed. Examination of the expression patterns in human stem cells, iPS cells and normal tissues showed that Oct4, Sox2, Klf4 and Nanog are expressed at similar levels in iPS cells and embryonic stem cells, and expression of all four transcription factors decreases after differentiation. Expression of Klf4 reduced to the least during differentiation, and Klf4 was found to be specifically expressed in several normal tissues, especially the salivary gland. In this paper, we systematically indentified the family proteins of the four transcription factors used to induce pluripotent stem cells, and then analyzed their evolution status, composed of those protein domains, alternative splicing translation, expression status and interaction networks. Those analysis could shed a light for further research of iPS.

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