The Stability of the Induced Epigenetic Programs

Table 2

Main breakthroughs regarding reprogramming and transdifferentiation of somatic cells. The need of oocytes and the low efficiency of nuclear transfer in humans have propitiated the search for alternative strategies to generate pluripotent cells. Induced pluripotent cells, initially obtained with retroviruses encoding Oct4, Sox2, Klf4 and c-Myc (OSKM), were considered unsafe for therapy due to the presence of viral integrations and the use of oncogenes Klf4 and c-Myc. Therefore, a major rush to develop non integrative methods and to avoid the use of oncogenes started. However, the finding that iPS cells have epigenetic and genetic aberrations suggests that these cells will need to be analyzed in detail before moving to the clinic.

Year	Breakthrough
1987	Fibroblast transdifferentiation to muscle cells [22]
1997	Pluripotent cells by nuclear transfer [23]
2006	Mouse iPS cells with OSKM retroviruses [24]
2007	Human iPS cells with OSKM retroviruses [25]
2008	IPS cells without c-Myc [26]
	iPS cells from neural stem cells with two factors [27]
	iPS cells with two factors and small molecules [28]
	iPS cells with non integrative viruses [29]
	Desease-specific iPS cells [30]
2009	iPS cells with proteins [31]
2010	iPS cells with RNA [32]
	Transdifferentiation of fibroblasts to neurons or to cardiomyocytes [33, 34]
	Transdifferentiation of fibroblasts to blood cells [35]
2011	iPS cells with miRNAs [36]
	iPS cells have epigenetic aberrations [37]
	iPS cells have genetic aberrations [38, 39]