Aberrant imprinting in mouse trophoblast stem cells established from somatic cell nuclear transfer-derived embryos

Hirose, Michiko; Hada, Masashi; Kamimura, Satoshi; Matoba, Shogo; Honda, Arata; Motomura, Kaori; Ogonuki, Narumi; Shawki, Hossam H.; Inoue, Kimiko; Takahashi, Satoru; Ogura, Atsuo

doi:10.1080/15592294.2018.1507199

Cited by 16 publications

(16 citation statements)

References 26 publications

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“…In the following, these clusters are referred to as the Sfmbt2 and Mirg miRNAs, respectively. The altered expression levels of these miRNAs might reflect the status of their host gene (Sfmbt2) and the imprinting center (intergenic differentially methylated region), respectively, because both are known to exhibit LOI in SCNT placentas 14 and SCNT-derived trophoblast stem cells (TSCs) 31 . Scatterplots showing the variations in the expression of all the miRNA genes between IVF and wild type SCNT placentas clearly distinguished the Sfmbt2 miRNAs and Mirg miRNAs from other genes based on their upregulation and downregulation, respectively (Fig.…”

Section: Resultsmentioning

confidence: 99%

Loss of H3K27me3 imprinting in the Sfmbt2 miRNA cluster causes enlargement of cloned mouse placentas

et al. 2020

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Somatic cell nuclear transfer (SCNT) in mammals is an inefficient process that is frequently associated with abnormal phenotypes, especially in placentas. Recent studies demonstrated that mouse SCNT placentas completely lack histone methylation (H3K27me3)-dependent imprinting, but how it affects placental development remains unclear. Here, we provide evidence that the loss of H3K27me3 imprinting is responsible for abnormal placental enlargement and low birth rates following SCNT, through upregulation of imprinted miRNAs. When we restore the normal paternal expression of H3K27me3-dependent imprinted genes (Sfmbt2, Gab1, and Slc38a4) in SCNT placentas by maternal knockout, the placentas remain enlarged. Intriguingly, correcting the expression of clustered miRNAs within the Sfmbt2 gene ameliorates the placental phenotype. Importantly, their target genes, which are confirmed to cause SCNT-like placental histology, recover their expression level. The birth rates increase about twofold. Thus, we identify loss of H3K27me3 imprinting as an epigenetic error that compromises embryo development following SCNT.

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Section: Resultsmentioning

confidence: 99%

Loss of H3K27me3 imprinting in the Sfmbt2 miRNA cluster causes enlargement of cloned mouse placentas

et al. 2020

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“…Previous studies indicated that epigenetic modifications were altered in cloned abnormal animals compared to naturally bred ones. Global hypo-acetylation, reduced DNA methylation in satellite I region, loss of imprinting (LOS), reduced histone methylation were reported in the somatic cell nuclear transfer derived animals [29,30,31]. Piglets derived by SCNT also showed a higher incidence of malformations and a higher death rate during the perinatal period [32].…”

Section: Discussionmentioning

confidence: 99%

Study on Hematological and Biochemical Characters of Cloned Duroc Pigs and Their Progeny

Shi

Luo

et al. 2019

Animals

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Simple SummaryCloning is the most promising technique for passing the excellent phenotypes of the best individuals in the population. Here we studied the effects of cloning on Duroc pig, which is the most popular sire used in pig production due to its good growth and meat quality. Understanding the changes of cloned Duroc pigs and their progenies is of great importance for animal breeding and public acceptance. The results of this study suggested that there were no difference in blood parameters between the cloned Duroc and the conventionally bred Duroc and their progenies.AbstractTo increase public understanding in cloned animals produced by somatic cell nuclear transfer technology, our previous study investigated the carcass trait and meat quality of the clones (paper accepted), and this study we further evaluate differences by investigating the blood parameters in cloned pigs and their progeny. We collected blood samples from the clones and conventionally bred non-clones and their progeny, and investigated their hematological and blood biochemical characters. Our results supported the hypothesis that there was no significant difference between clones and non-clones, or their progeny. Taken together, the data demonstrated that the clones or their progeny were similar with their controls in terms of blood parameters, although there were still other kinds of disorders, such as abnormal DNA methylation or histone modifications that needs further investigation. The data in this study agreed that cloning technique could be used to preserve and enlarge the genetics of the superior boars in pig breeding industry, especially in facing of the deadly threat of African Swine fever happened in China.

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“…The unusual DNA methylation pattern mostly exists on the satellite sequence, long terminal repeat sequence, long dispersed elements (LINEs), and imprinted control region (ICR). Trophoblast cells in SCNT blastocysts are hypermethylated in intergenic differentially methylated regions, which are associated with subsequent abnormal placental development [30]. Treatment with a methyltransferase inhibitor and interference of Dnmts have been used to reduce the higher DNA methylation level, and this strategy effectively improves the SCNT efficiency [28].…”

Section: Dna Methylationmentioning

confidence: 99%

Insights into the roles of sperm in animal cloning

Wang

Zhang

et al. 2020

Stem Cell Res Ther

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Somatic cell nuclear transfer (SCNT) has shown a wide application in the generation of transgenic animals, protection of endangered animals, and therapeutic cloning. However, the efficiency of SCNT remains very low due to some poorly characterized key factors. Compared with fertilized embryos, somatic donor cells lack some important components of sperm, such as sperm small noncoding RNA (sncRNA) and proteins. Loss of these factors is considered an important reason for the abnormal development of SCNT embryo. This study focused on recent advances of SCNT and the roles of sperm in development. Sperm-derived factors play an important role in nucleus reprogramming and cytoskeleton remodeling during SCNT embryo development. Hence, considering the role of sperm may provide a new strategy for improving cloning efficiency.

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Aberrant imprinting in mouse trophoblast stem cells established from somatic cell nuclear transfer-derived embryos

Cited by 16 publications

References 26 publications

Loss of H3K27me3 imprinting in the Sfmbt2 miRNA cluster causes enlargement of cloned mouse placentas

Loss of H3K27me3 imprinting in the Sfmbt2 miRNA cluster causes enlargement of cloned mouse placentas

Study on Hematological and Biochemical Characters of Cloned Duroc Pigs and Their Progeny

Insights into the roles of sperm in animal cloning

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