An in silico approach - reprogramming the somatic cells into iPS cells by transcriptional regulation of promoter region of OSKM regulatory network


Abstract:
The stem cell has given tremendous applications in genetic and molecular medicine. However, researches on stem cells have seen decreased progress in finding new applications because of ethical issues. Recent scientific achievements in genetic and molecular therapies have provided unprecedented opportunities for advances in biomedical research and thus have given an opportunity for in silico working capabilities. One such advancement is reprogramming of a gene expression within a cell by targeting the desired gene of network. Such reprogramming method was efficiently applied in creating the induced pluripotent stem (iPS) cells from somatic cells by regulating the expression of pluripotent genes, such as Oct4, Sox2, Klf4 and c-Myc (OSKM). We found some regulating factors, such as zinc finger protein, which can precisely bind the targeted gene of interest with more specific binding in nature. In silico tools, such as Gene2Promoter and Mathinspector have identified the suitable promoter sequences of OSKM gene network with respective transcriptional start site sequence. Transcriptional start site sequences of each gene helps us to identify its location in the genome of a somatic cell. Minimum of 4 triplet sequences of each individual gene were used to identify the specific zinc finger protein, which is binding to the transcriptional start site of the promoter region of the gene. Obtained zinc finger protein binding to the transcriptional start site of the gene was analysed for binding affinity ratio with the triplet sequences of the gene by ELISA graph. Finally obtained zinc finger protein sequences were reported to regulate the pluripotent gene OSKM regulatory networks and induce the cellular pathway to produce iPS cells (induced pluripotent stem cells).

Keywords:
OSKM; Regulatory networks; Reprogramming; Stemness; Zinc finger protein; iPS cells

Full text PDF | Download PDF



How to cite this article:
Baskar V, Madhan R, Selvakumar K, Srinivasan G, Amutha K, Yagamathi K. An in silico approach - reprogramming the somatic cells into iPS cells by transcriptional regulation of promoter region of OSKM regulatory network. Journal of Biological and Information Sciences. 2012. 1 (3). 42-48.
Available from: http://archive.biolim.org/jbis/read/BOJ001A0011.