Abstract
Mammalian oocytes can reprogram differentiated somatic cells into a totipotent state through somatic cell nuclear transfer (SCNT), which is known as cloning. Although many mammalian species have been successfully cloned, the majority of cloned embryos failed to develop to term, resulting in the overall cloning efficiency being still low. There are many factors contributing to the cloning success. Aberrant epigenetic reprogramming is a major cause for the developmental failure of cloned embryos and abnormalities in the cloned offspring. Numerous research groups attempted multiple strategies to technically improve each step of the SCNT procedure and rescue abnormal epigenetic reprogramming by modulating DNA methylation and histone modifications, overexpression or repression of embryonic-related genes, etc. Here, we review the recent approaches for technical SCNT improvement and ameliorating epigenetic modifications in donor cells, oocytes, and cloned embryos in order to enhance cloning efficiency.
Highlights
Somatic cell nuclear transfer (SCNT) or cloning involves transferring a donor cell into an enucleated oocyte, enabling the reprogramming of terminally differentiated cells into totipotent cells [1]
As a whole donor cell is transferred into an enucleated oocyte during SCNT, is the nuclear genome passed onto the oocyte and mitochondria accompanying the donor cell are transferred as well [83,84]
The mitochondrial DNA (mtDNA) depletion of the donor cells combined with Histone deacetylase inhibitors (HDACi) treatment of cloned embryos positively modulated the expression levels of genes involved in DNA methylation, embryonic formation, and embryonic development
Summary
Somatic cell nuclear transfer (SCNT) or cloning involves transferring a donor cell into an enucleated oocyte, enabling the reprogramming of terminally differentiated cells into totipotent cells [1]. Aberrant epigenetic modifications have been found in cloned embryos, which affect low cloning efficiency, abnormal cloned embryo phenotype, and low viability cloned animals (reviewed by [17,18]) Epigenetic modifications such as DNA methylation, histone acetylation, histone methylation, genomic imprinting, and X-chromosome inactivation are crucial events for the nuclear reprogramming process (reviewed by [15,19]). Epigenetic modifications of the donor cell nuclei or cloned embryo could increase accessibility for reprogramming [20] Epigenetic modifications such as DNA methylation and histone modifications are key factors to regulate gene expression, and they play an important role on embryonic development [21,22]. We discussed the current knowledge of improving the SCNT procedure, in vitro maturation (IVM), in vitro culture (IVC) media, modification of donor cells, oocytes and cloned embryos, and amelioration of epigenetic status during SCNT in order to increase cloning efficiency
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