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Reprogramming refers to erasure and remodeling of epigenetic marks, such as DNA methylation, during mammalian development. After fertilization some cells of the newly formed embryo migrate to the germinal ridge and will eventually become the germ cells (sperm and oocytes). Due to the phenomenon of genomic imprinting, maternal and paternal genomes are differentially marked and must be properly reprogrammed every time they pass through the germline. Therefore, during the process of gametogenesis the primordial germ cells must have their original biparental DNA methylation patterns erased and re-established based on the sex of the transmitting parent.
After fertilization the paternal and maternal genomes are once again demethylated and remethylated (except for differentially methylated regions associated with imprinted genes). This reprogramming is likely required for totipotency of the newly formed embryo and erasure of acquired epigenetic changes. In vitro manipulation of pre-implantation embryos has been shown to disrupt methylation patterns at imprinted loci and plays a crucial role in cloned animals.
The first person to successfully demonstrate reprogramming was Sir John Gurdon, who in 1962 demonstrated that differentiated somatic cells could be reprogrammed back into an embryonic state when he managed to obtain swimming tadpoles following the transfer of differentiated intestinal epithelial cells into enucleated frog eggs. For this achievement he received the 2012 Nobel Prize in Medicine alongside Shinya Yamanaka. Dr. Yamanaka was the first to demonstrate that this somatic cell nuclear transfer or oocyte-based reprogramming process (see below), that Dr. Gurdon discovered, could be recapitulated by defined factors (OCT4, SOX2, KLF4 and cMYC) to generate induced pluripotent stem cells (iPSCs).
Somatic cell nuclear transfer
During somatic cell nuclear transfer, the oocyte turns off tissue specific genes in the Somatic cell nucleus and turns back on embryonic specific genes.
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