1. Contributions to Stem Cell research
  2. Sources

            Embryonic stem (ES) cells are made from the inner cell mass of a blastocyst and can be produced in culture in an undifferentiated state which means that the cells are able to generate any cell type [1]. These ES cells have the property to keep their capacity of self-renewal but at the same time have the potential to form cells for the endoderm, mesoderm, or ectoderm [2]. Recently, there have been three primary transcription factors which have emerged. They have been named OCT4, SOX2, and NANOG which all play a role in determining the end fate of ES cells [1], [2]. Understanding the role of these transcription factors can help to explain the phenotypes that are seen during regulation of these factors. Depending on the activation or inactivation of each of these transcription factors will determine whether the ES cells remain pluripotent due to positive regulation of their own genes or if they become differentiated [1], [2].

            Kornberg’s work has helped to lay out exactly what is happening in transcription. By combining his work with the role of transcription factors determining ES cell fate, we can get detailed mechanism as to how these pluripotent cells can be stimulated to differentiate into different cell types [1]. Also, scientists can use Kornberg’s work to determine what target genes are going to be expressed when combinations of the three transcription factors are expressed [2].

            Therefore, Kornberg’s work can be combined with ES cell research and help to explain transcriptional regulation of developing cells. If we understand how transcription works, through Kornberg, we are able to figure out how transcription will be regulated in the early developmental stages and that will be able to give us specific development and embryonic stem cell properties [3].

[1] Boyer, L.A.; Lee, T.I.; Cole, M.F.; Johnstone, S.E.; Levine, S.S.; Zucker, J.P.; Guenther, M.G.; Kumar, R.M.; Murray, H.L.; Jenner, R.G.; Gifford, D.K.; Melton, D.A.; Jaenisch, R.; Young, R.A. Core Transcriptional Regulatory Circuitry in Human Embryonic Stem Cells. Cell. 23 September, 2005. 122, 947-956.

[2] Chickarmane, V.; Troein, U.A.; Sauro, H.M.; Peterson, C. Transcriptional Dynamic of the Embryonic Stem Cell Switch. PloS Computational Biology. September 2006. 2, 1080-1092.

[3] Zhang, W.; Walker, E.; Tramplin, O.J.; Rossant, J.; Stanford, W.L.; Hughes, T.R. Zfp206 regulates ES cell gene expression and differentiation. Nucleic Acids Research. 13 September 2006. 34, 4780-4790.

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Written by:

Mitchell Springer

Stem Cell Contribution