Embryonic Development following Somatic Cell Nuclear Transfer Impeded by Persisting Histone Methylation

Matoba, Shogo; Liu, Yuting; Lu, Falong; Iwabuchi, Kumiko A.; Shen, Li; Inoue, Atsuyuki; Zhang, Yi

doi:10.1016/j.cell.2014.09.055

Cited by 412 publications

(614 citation statements)

References 47 publications

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“…However, the improvement of embryonic development could be due to the changes of complicated gene networks, rather than a single gene. For example, in the recent study, it was found that numerous candidate genes expressed differently after regulation of H3K9me3, but most of these genes function were unclear (Matoba et al 2014). So it was great difficulty, if possible, to determine which genes were responsible for the improvement of embryonic development.…”

Section: Discussionmentioning

confidence: 99%

“…And more recently, H3K9me3 was identified as a critical epigenetic barrier in SCNT reprogramming. The reprogramming resistant regions (RRRs) that could not be activated in cloned embryos as that in fertilized embryos were enriched for H3K9me3 in donor cells, and its removal by deletion of H3K9me3 methylase in donor cells and by ectopically expressed H3K9me3 demethylase in cloned emryos not only reactivated the majority of RRRs, but greatly improved SCNT efficiency as well (Matoba et al 2014).…”

Section: Introductionmentioning

confidence: 99%

“…Similarly, abnormal epigenetics reprogramming also often occur in these areas during iPS induction, and the reprogramming efficiency could be improved by regulating these epigenetic status both in SCNT and iPS (Kishigami et al 2006, Huangfu et al 2008, Onder et al 2012, Huan et al 2013, Matoba et al 2014.…”

Section: Introductionmentioning

confidence: 99%

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Histone H3 lysine 27 trimethylation acts as an epigenetic barrier in porcine nuclear reprogramming

et al. 2016

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Aberrant epigenetic reprogramming is the main obstacle to the development of somatic cell nuclear transfer (SCNT) embryos and the generation of induced pluripotent stem (iPS) cells, which results in the low reprogramming efficiencies of SCNT and iPS. Histone H3 lysine 27 trimethylation (H3K27me3), as a repressive epigenetic mark, plays important roles in mammalian development and iPS induction. However, the reprogramming of H3K27me3 in pig remains elusive. In this study, we showed that H3K27me3 levels in porcine early cloned embryos were higher than that in IVF embryos. Then GSK126 and GSK-J4, two small molecule inhibitors of H3K27me3 methylase (EZH2) and demethylases (UTX/JMJD3), were used to regulate the H3K27me3 level. The results showed that H3K27me3 level was reduced in cloned embryos after treatment of PEF with 0.75 mM GSK126 for 48 h, incubation of one-cell reconstructed oocytes with 0.1 mM GSK126 and injection of antibody for EZH2 into oocyte. Meanwhile, the development of the cloned embryos was significantly improved after these treatments. On the contrary, GSK-J4 treatment increased the H3K27me3 level in cloned embryos and decreased the cloned embryonic development. Furthermore, iPS efficiency was both increased after reducing the H3K27me3 level in donor cells and in early reprogramming phase. In summary, our results suggest that H3K27me3 acts as an epigenetic barrier in SCNT and iPS reprogramming, and reduction of H3K27me3 level in donor cells and in early reprogramming phase can enhance both porcine SCNT and iPS efficiency.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Histone H3 lysine 27 trimethylation acts as an epigenetic barrier in porcine nuclear reprogramming

et al. 2016

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“…Significant advancements have been accomplished in mouse SCNT; however, the simplest approach, the treatment with TSA, does not work in large animals, or better (Sangalli et al, 2012). Of the other ones, RNAi-mediated down-regulation of Xist (Matoba et al, 2011) and the depletion of H3K9 methyl-transferases (Matoba et al, 2014), the first one has a sex bias, working only in female cells, while the second is technically challenging, and hardly accomplishable in large animals, where the molecular biology tool are less advanced. …”

Section: Background: Mousementioning

confidence: 99%

“…2ii), also proved to significantly increase the proportion of offspring. The latest reprogramming efficiency, always developed for the mouse, is the depletion of H3K9me3 methylation in somatic cells before nuclear transfer (Matoba et al, 2014). Tri-methylated H3K9 is a epigenomic landmark conferring resistance to nuclear reprogramming, thus, its genome-wipe up through the exogenous expression of H3Kme9 demethylase increases genome accessibility to reprogramming mechanisms, enhancing in turn cloning efficiency (Matoba et al, 2014) (Fig.…”

Section: Background: Mousementioning

confidence: 99%

Alternative strategies for nuclear reprogramming in Somatic Cell Nuclear transfer (SCNT)

Loi¹,

Iuso²,

Toschi³

et al. 2017

Anim Reprod

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Twenty years passed by since the production of Dolly the sheep, but despite significant technical progress has been achieved in the manipulation procedures, the proportion of offspring following transfer of SCNT embryos has remained almost unchanged in farm animals. Remarkable progress has been obtained instead in laboratory animals, particularly by Japanese Groups, in the mouse. However, the nuclear reprogramming strategies tested in mouse do not always work in farm animals, and others are difficult to be implemented, for require complicated molecular biology tools unavailable yet in large animals. In this review we put in contest the previous work done in farm and laboratory animals with recent achievements obtained in our laboratory, and we also indicate a road map to increase the reliability of SCNT procedures.

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Nuclear Transfer from Cell Lines

Wakayama

Wells

2023

Encyclopedia of Life Sciences

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The production of cloned animals following nuclear transfer, using somatic cells grown in culture, represents a remarkable feat of developmental biology. It demonstrates the potential of a differentiated nucleus to be reprogrammed back to an embryonic state when exposed to a suitable cytoplasmic environment, such as that of an enucleated oocyte. It involves fundamental changes to the patterns of DNA methylation and chromatin modification imposed on a specialised nucleus to enable the precise temporal‐spatial sequence of gene expression necessary for normal embryogenesis. However, reprogramming is often incomplete with development going astray, resulting in a continuum of embryo, fetal and postnatal mortality. The majority of the clones that do survive to adulthood, and their sexually derived progeny, do, however, appear normal. This provides encouragement for the practical applications of nuclear cloning in the fields of agriculture, animal conservation and biomedicine. Key Concepts The cytoplasm of mature oocytes has the potential to reprogramme the epigenetic state and pattern of gene expression of differentiated donor cells back to that of an embryo following nuclear transfer, enabling the production of cloned animals. The success rate of cloned animals is more influenced by differences in nuclear transfer method than by the type of animal or cell. Because cultured cells can be multiplied, cryopreserved, andused at any time, cloning animals from cultured cells has many advantages overusing fresh cells collected from animals. Using nuclear transfer technology, embryonic stem (ES) cell lines can be generated from somatic cells, and cloned animals can be produced using these cultured cells as donors. Epigenetic abnormalities frequently occur in cloned animals, but the next generation born from the cloned parents are normal and can be used without problems in livestock production. Cloning technology could help save endangered species.

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Embryonic Development following Somatic Cell Nuclear Transfer Impeded by Persisting Histone Methylation

Cited by 412 publications

References 47 publications

Histone H3 lysine 27 trimethylation acts as an epigenetic barrier in porcine nuclear reprogramming

Histone H3 lysine 27 trimethylation acts as an epigenetic barrier in porcine nuclear reprogramming

Alternative strategies for nuclear reprogramming in Somatic Cell Nuclear transfer (SCNT)

Nuclear Transfer from Cell Lines

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