Genome stabilization by RAD51‐stimulatory compound 1 enhances efficiency of somatic cell nuclear transfer‐mediated reprogramming and full‐term development of cloned mouse embryos

Lee, Ah Reum; Park, Jihoon; Shim, Sung Han; Hong, Kwonho; La, Hyeonwoo; Park, Kyung-Soon; Lee, Dong Ryul

doi:10.1111/cpr.13059

Cited by 7 publications

(6 citation statements)

References 53 publications

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“…To repair genetic instability or DSBs, cloned mouse embryos were treated with RAD 51-stimulatory compound 1 (RS-1), which is an activator of Rad51. RS-1 treatment recovered RAD51 activity, overcame developmental arrest at the two-cell stage, and also increased blastocyst formation and offspring rates in cloned mouse embryos [237]. A combination of Kdm4a mRNA injection and RS-1 treatment significantly increased the blastocyst rates of cloned mouse embryos (82.5%) when compared to those of only Kdm4a injection (66.0%), only RS-1 treatment (65.9%), and control cloned embryos (35.1%) [237].…”

Section: Alternative Methods For Cloning Efficiency Improvementmentioning

confidence: 90%

“…Rad51 homologous 1 (RAD51) is a DNA-binding protein that maintains genome stability and regulates signaling proteins to control the DNA damage response, replication, repair, and recombination (reviewed by [236]). The activity of RAD51 and DSBs were lower in cloned mouse embryos than IVF embryos, which caused a decrease in DNA repair and an increase in genetic instability, resulting in the developmental arrest of cloned embryos [237]. To repair genetic instability or DSBs, cloned mouse embryos were treated with RAD 51-stimulatory compound 1 (RS-1), which is an activator of Rad51.…”

Section: Alternative Methods For Cloning Efficiency Improvementmentioning

confidence: 99%

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Strategies to Improve the Efficiency of Somatic Cell Nuclear Transfer

Srirattana

Kaneda

Parnpai

2022

IJMS

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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.

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Section: Alternative Methods For Cloning Efficiency Improvementmentioning

confidence: 90%

Section: Alternative Methods For Cloning Efficiency Improvementmentioning

confidence: 99%

Strategies to Improve the Efficiency of Somatic Cell Nuclear Transfer

Srirattana

Kaneda

Parnpai

2022

IJMS

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“…Low success rates have been reported for reproductive cloning resulting in only 5–10% of reprogrammed embryos yielding viable offspring, with many factors affecting this success rate ( Long et al 2014 ). These factors include DNA damage, which can be improved by upregulating modulators of the DNA damage response ( Lee et al 2021 ), the cell type used for nuclear donation ( Inoue et al 2005 , Liu et al 2015 , Lee et al 2019 ) and the mismatch of mitochondrial DNA between donor cell and recipient oocyte ( Takeda 2019 , Mrowiec et al 2021 ). Epigenetic processes may also affect DNA replication and transcription ( Gouveia et al 2020 ).…”

Section: Somatic Cell Cryopreservation and Advanced Assisted Reproduc...mentioning

confidence: 99%

Resurrecting biodiversity: advanced assisted reproductive technologies and biobanking

Bolton¹,

Mooney²,

Pettit

et al. 2022

Reproduction and Fertility

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Biodiversity: the variety of all living organisms on Earth is essential for human survival. However, anthropogenic activities are causing the sixth mass extinction, threatening even our own species. For many animals, dwindling numbers are becoming fragmented populations with low genetic diversity, threatening long-term species viability. With extinction rates 1,000-10,000 times greater than is natural, ex situ and in situ conservation programmes need additional support to save species. The indefinite storage of cryopreserved (-196oC) viable cells and tissues (cryobanking), followed by assisted or advanced assisted reproductive technology (ART: utilisation of oocytes and spermatozoa to generate offspring; aART: utilisation of somatic cell genetic material to generate offspring), may be the only hope for species long-term survival. As such, cryobanking should be considered a necessity for all future conservation strategies. Following cryopreservation, ART/aART can be used to reinstate lost genetics back into a population, resurrecting biodiversity. However, for this to be successful, species-specific protocol optimisation and increased knowledge of basic biology for many taxa is required. Current ART/aART is primarily focused on mammalian taxa, however, this needs to be extended to all, including to some of the most endangered: amphibians. Gamete, reproductive tissue and somatic cell cryobanking can fill the gap between losing genetic diversity today, and future technological developments. This review explores species prioritisation for cryobanking and the successes and challenges of cryopreservation and multiple ARTs/aARTs. We discuss the value of cryobanking before more species are lost and the potential of advanced reproductive technologies not only to halt, but reverse biodiversity loss.

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“…In our preliminary study, we examined the effect of RS-1, a Rad51 activator, on genome variation during direct differentiation (treatment for 24 h during differentiation on day three) into PSC-MPCs. The concentration was chosen on the basis of a preliminary toxicity test (data not shown) and our previous report [23]. As shown in Supplementary Figure S6, the addition of 10 µM RS-1 reduced the average number of de novo CNV variations (at >100 kbp resolution) at passage 12 (p < 0.05).…”

Section: Array Cgh Of Scnt-pscs-mpcsmentioning

confidence: 99%

“…Additionally, HR may contribute to genomic stability during mouse ESC differentiation. In fact, DNA breaks are repaired by homologous recombination (HR)-mediated proteins, such as Rad51 homologous 1 (Rad51) and Rad52, and this repair diminishes the cell death rate [22,23]. Therefore, to extend the efficacy of SCNT-PSC-MPCs in cell therapy, we aimed to enhance an efficient medium using a Rad51 activator and the direct differentiation method, bypassing EB formation, and we analyzed not only their proliferative and differential potential but also their genetic stability during differentiation and cultivation in vitro.…”

Section: Introductionmentioning

confidence: 99%

Rapid Production and Genetic Stability of Human Mesenchymal Progenitor Cells Derived from Human Somatic Cell Nuclear Transfer-Derived Pluripotent Stem Cells

Jung

Lee

et al. 2021

IJMS

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Pluripotent stem cell-derived mesenchymal progenitor cells (PSC-MPCs) are primarily derived through two main methods: three-dimensional (3D) embryoid body-platform (EB formation) and the 2D direct differentiation method. We recently established somatic cell nuclear transfer (SCNT)-PSC lines and showed their stemness. In the present study, we produced SCNT-PSC-MPCs using a novel direct differentiation method, and the characteristics, gene expression, and genetic stability of these MPCs were compared with those derived through EB formation. The recovery and purification of SCNT-PSC-Direct-MPCs were significantly accelerated compared to those of the SCNT-PSC-EB-MPCs, but both types of MPCs expressed typical surface markers and exhibited similar proliferation and differentiation potentials. Additionally, the analysis of gene expression patterns using microarrays showed very similar patterns. Moreover, array CGH analysis showed that both SCNT-PSC-Direct-MPCs and SCNT-PSC-EB-MPCs exhibited no significant differences in copy number variation (CNV) or single-nucleotide polymorphism (SNP) frequency. These results indicate that SCNT-PSC-Direct-MPCs exhibited high genetic stability even after rapid differentiation into MPCs, and the rate at which directly derived MPCs reached a sufficient number was higher than that of MPCs derived through the EB method. Therefore, we suggest that the direct method of differentiating MPCs from SCNT-PSCs can improve the efficacy of SCNT-PSCs applied to allogeneic transplantation.

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Genome stabilization by RAD51‐stimulatory compound 1 enhances efficiency of somatic cell nuclear transfer‐mediated reprogramming and full‐term development of cloned mouse embryos

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 7 publications

References 53 publications

Strategies to Improve the Efficiency of Somatic Cell Nuclear Transfer

Strategies to Improve the Efficiency of Somatic Cell Nuclear Transfer

Resurrecting biodiversity: advanced assisted reproductive technologies and biobanking

Rapid Production and Genetic Stability of Human Mesenchymal Progenitor Cells Derived from Human Somatic Cell Nuclear Transfer-Derived Pluripotent Stem Cells

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