Abstract
Somatic cell nuclear transfer (SCNT) enables terminally differentiated somatic cells to gain totipotency. Many species are successfully cloned up to date, including nonhuman primate. With this technology, not only the protection of endangered animals but also human therapeutics is going to be a reality. However, the low efficiency of the SCNT-mediated reprogramming and the defects of extraembryonic tissues as well as abnormalities of cloned individuals limit the application of reproductive cloning on animals. Also, due to the scarcity of human oocytes, low efficiency of blastocyst development and embryonic stem cell line derivation from nuclear transfer embryo (ntESCs), it is far away from the application of this technology on human therapeutics to date. In recent years, multiple epigenetic barriers are reported, which gives us clues to improve reprogramming efficiency. Here, we reviewed the reprogramming process and reprogramming defects of several important epigenetic marks and highlighted epigenetic barriers that may lead to the aberrant reprogramming. Finally, we give our insights into improving the efficiency and quality of SCNT-mediated reprogramming.
Highlights
Somatic cell nuclear transfer (SCNT), first demonstrated by Gurdon in 1962 [1], is a technology to form reconstructed embryos by injecting donor nucleus into enucleated oocytes and generate cloned animals
SCNT provides the only way to reprogram somatic cells into totipotent embryos and generate viable animals [9, 109, 110]
After injected into enucleated oocytes, the donor nucleus quickly undergoes nuclear membrane breakdown followed by premature chromosome condensation (PCC), which is triggered by the M-phase-prompting factors (MPFs) stored at ooplasm [111]
Summary
Somatic cell nuclear transfer (SCNT), first demonstrated by Gurdon in 1962 [1], is a technology to form reconstructed embryos by injecting donor nucleus into enucleated oocytes and generate cloned animals. SCNT technology is widely used to acquire nuclear transfer embryonic stem cells (ntESCs), which is called therapeutic cloning [8,9,10]. Low efficiency (Table 1) as well as defects in extraembryonic tissues and cloned individuals in many species impedes the application of SCNT technology, which has been fully reviewed [4, 15, 16]. For the most used animal model, mouse, SCNT embryos are usually arrested at 2-cell and 4-cell stages [17, 18]. 4 6 45 (transferred with 2-cell embryos) 47 (transferred with cleaved embryos) 110 (2- and 8-cell stage embryos were transferred) 72 371 (transferred with 4-cell stage embryos)
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