Editing Cellular differentiation (section)

====Pioneer factors (Oct4, Sox2, Nanog)====
Three transcription factors, OCT4, SOX2, and [[Homeobox protein NANOG|NANOG]] – the first two of which are used in induced pluripotent stem cell (iPSC) reprogramming, along with [[Klf4]] and [[c-Myc]] – are highly expressed in undifferentiated embryonic stem cells and are necessary for the maintenance of their [[pluripotency]].<ref name = "Christophersen">{{cite journal | vauthors = Christophersen NS, Helin K | title = Epigenetic control of embryonic stem cell fate | journal = The Journal of Experimental Medicine | volume = 207 | issue = 11 | pages = 2287–2295 | date = October 2010 | pmid = 20975044 | pmc = 2964577 | doi = 10.1084/jem.20101438 }}</ref> It is thought that they achieve this through alterations in [[chromatin]] structure, such as [[histone modification]] and DNA methylation, to restrict or permit the transcription of target genes. While highly expressed, their levels require a precise balance to maintain pluripotency, perturbation of which will promote differentiation towards different lineages based on how the gene expression levels change. Differential regulation of [[Oct-4]] and [[SOX2]] levels have been shown to precede germ layer fate selection.<ref name="ReferenceA">{{cite journal | vauthors = Thomson M, Liu SJ, Zou LN, Smith Z, Meissner A, Ramanathan S | title = Pluripotency factors in embryonic stem cells regulate differentiation into germ layers | journal = Cell | volume = 145 | issue = 6 | pages = 875–889 | date = June 2011 | pmid = 21663792 | pmc = 5603300 | doi = 10.1016/j.cell.2011.05.017 }}</ref> Increased levels of Oct4 and decreased levels of Sox2 promote a [[Gastrulation|mesendodermal]] fate, with Oct4 actively suppressing genes associated with a neural [[neurulation|ectodermal]] fate. Similarly, increased levels of Sox2 and decreased levels of Oct4 promote differentiation towards a neural ectodermal fate, with Sox2 inhibiting differentiation towards a mesendodermal fate. Regardless of the lineage cells differentiate down, suppression of NANOG has been identified as a necessary prerequisite for differentiation.<ref name="ReferenceA"/>