Some processes in Stem cell differentiation yet to be addressed

Stem cell differentiationWhile considering stem cell differentiation, researchers have found theoretically the working of many models such as “OCT4-SOX2-NANOG system, lineage determination between trophectoderm and endoderm and the later differentiation of cells into any one of three mesenchymal lineages under the regulation of the master transcription factors RUNX2, SOX9 and PPAR-g.” (John A Fozard et.al.)

 

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However, it is still to find the interaction between multiple pathways. Moreover, many of the important processes implicated in cell differentiation have to be determined yet, especially the detailed mechanism involved in the later stages of cell differentiation into specific phenotypes. (John A Fozard et.al.)  Role of DNA methylation pattern in the regulation of developmental genes through histone modification is still not much clear. However, it has been suggested that DNA methylation is involved in the tissue-specific gene expression in differentiation process. (Takayuki Isagawa et. al.)

Transcriptional pausing is the process in which there is only transcription of genes without its elongation process. The physiological significance of transcriptional pausing is still to work on. However, it has been suggested that transcriptional pausing plays an important role in the altering the gene expression during the differentiation of pluripotent human embryonic stem cells. Researchers have found that TGF-beta superfamily and the Wnt/β-catenin pathways strongly regulate the transcription process but their use in the independent regulation of initiation and elongation needs further work. These two pathways are found to play an important role in the induction of mesoderm, i.e. the middle of the three cell layers in an embryo, through coordinated signaling. (Jonathan L. Golob et. al.)

Reference:

John A Fozard, Glen R Kirkham, Lee DK Buttery, John R King,Oliver E Jensen and Helen M Byrne, (2012). Techniques for analyzing pattern formation in populations of stem cells and their progeny. BMC Bioinformatics, 12, 396

Takayuki Isagawa, Genta Nagae, Nobuaki Shiraki, Takanori Fujita, Noriko Sato, Shumpei Ishikawa , Shoen Kume, Hiroyuki Aburatani, (2011). DNA Methylation Profiling of Embryonic Stem Cell Differentiation into the Three Germ Layers. PLoS ONE, doi:10.1371/journal.pone.0026052

Jonathan L. Golob, Roshan M. Kumar, Matthew G. Guenther, Lil M. Pabon, Gabriel A. Pratt, Jeanne F. Loring, Louise C. Laurent, Richard A. Young, Charles E. Murry, (2011). Evidence That Gene Activation and Silencing during Stem Cell Differentiation Requires a Transcriptionally Paused Intermediate State. PLoS ONE, doi:10.1371/journal.pone.0022416

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