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

Cytotechnology | 2014

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.

Pubmed ID: 24129607 RIS Download

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UCSC Genome Browser (tool)

RRID:SCR_005780

Portal to interactively visualize genomic data. Provides reference sequences and working draft assemblies for collection of genomes and access to ENCODE and Neanderthal projects. Includes collection of vertebrate and model organism assemblies and annotations, along with suite of tools for viewing, analyzing and downloading data.

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BLASTX (tool)

RRID:SCR_001653

Web application to search protein databases using a translated nucleotide query. Translated BLAST services are useful when trying to find homologous proteins to a nucleotide coding region. Blastx compares translational products of the nucleotide query sequence to a protein database. Because blastx translates the query sequence in all six reading frames and provides combined significance statistics for hits to different frames, it is particularly useful when the reading frame of the query sequence is unknown or it contains errors that may lead to frame shifts or other coding errors. Thus blastx is often the first analysis performed with a newly determined nucleotide sequence and is used extensively in analyzing EST sequences. This search is more sensitive than nucleotide blast since the comparison is performed at the protein level.

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