TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos

Liu, Xin; Chen, Lu; Wang, Tao; Zhou, Jilong; Li, Zhekun; Bu, Guowei; Zhang, Jingjing; Yin, Shu-Yuan; Wu, Dan-Ya; Dou, Cheng-Li; Xu, Tian; He, Hainan; Zhu, Wei; Yu, Longtao; Liu, Zhiting; Zhang, Xia; Chen, Zhenxia; Miao, Yi‐Liang

doi:10.1016/j.stemcr.2021.09.012

Cited by 16 publications

(14 citation statements)

References 48 publications

(82 reference statements)

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“…Incomplete DNA demethylation and abnormal histone modification in cloned embryos are important characteristics of incomplete reprogramming [2]. Previous studies reported abnormalities in 5-mC and H3K9me3 processing in cloned embryos of mice, cattle, and other animals compared to fertilized embryos [4,40,41]. Here, we found higher levels of 5-mC and H3K9me3 in cloned rabbit embryos than in fertilized embryos.…”

Section: Discussionsupporting

confidence: 59%

“…In mammals, the oocyte is fertilized by the sperm to form a zygote, in which the parent genomes undergo epigenetic modifications and reprogramming under the action of some specific factors to initiate development of the embryo [3]. Abnormal reprogramming of a cloned embryo is considered to be the major reason for low cloning efficiency, and the absence of regulatory factors derived from sperm may be an important cause of abnormal reprogramming [4,5]. A number of recent studies have shown that sperm-derived small RNAs, proteins, and post-translational modifications play a very important role in the formation of the male and female pronuclei, embryonic cleavage, zygote gene conversion, embryonic cell differentiation, and embryo attachment [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

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Sperm‐borne proteins improve rabbit cloning efficiency via regulating embryonic cleavage and epigenetics

Cao

Zhang

et al. 2022

Proteomics

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Somatic cell nuclear transfer (SCNT) shows great application value in the generation of transgenic animals, protection of endangered species, and therapeutic cloning.However, the cloning efficiency is still very low, which greatly restricts its application. Compared to fertilized embryos, cloned embryos lack the sperm proteins, which are considered to play an important role in embryonic development. Here, we compared the sperm proteome, with that of donor fibroblasts and oocytes, and identified 342 proteins unique to sperm, with 42 being highly expressed. The 384 proteins were mainly enriched in the categories of post-translational modification and cytoskeletal arrangement. Extracts of soluble sperm or fibroblast proteins were injected into cloned embryos, and the result showed that injection of sperm protein significantly inhibited abnormal embryonic cleavage, significantly decreased the level of trimethylated histone H3 Lys9 (H3K9me3) and the apoptotic index, and increased the inner cell mass (ICM)-to-trophectoderm (TE) ratio. More importantly, the sperm proteins also significantly enhanced the birthrate. The results of in vitro and in vivo experiments demonstrate that sperm-derived proteins improve embryo cloning efficiency. Our findings not only provide new insights into ways to overcome low cloning efficiency, but also add to the understanding of sperm protein function.

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Section: Discussionsupporting

confidence: 59%

Section: Introductionmentioning

confidence: 99%

Sperm‐borne proteins improve rabbit cloning efficiency via regulating embryonic cleavage and epigenetics

Cao

Zhang

et al. 2022

Proteomics

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“…Somatic cell nuclear transfer is an essential cloning tool for biomedical and epigenetic research (Srirattana et al, 2022. This method enables significant development in biomedicine and disease modeling, where genome-edited mammals can be bred and used for disease research, transplantation, or to protect endangered species (Tian et al, 2003; Grzybek et al, 2017b; Fatira et al, 2018; Liu et al, 2021; Yue et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Methylation genome wide profiling in lowly and highly efficient adipose somatic cell nuclear transfer in pigs

Grzybek

Flisikowski

Giles

et al. 2022

Preprint

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Swine is a common model organism for biomedical research. Epigenetic reprogramming in SCNT embryos does not fully recapitulate the natural DNA demethylation events at fertilisation. This study aimed to conduct a genome-wide methylation profiling to detect differentially methylated regions (DMRs) responsible for epigenetic differences in stem cells that displayed high and low efficiency of SCNT and to elucidate the low efficiency of cloning rate in pigs. Adipose tissue mesenchymal stem cells (AMSC)s lines were isolated from adipose tissue of adult male pigs (n=20; high-efficiency cells=10; low efficiency cells= 10). Reduced representation bisulfite sequencing (RRBS) was performed on an Illumina HiSeq1500. Paired-end reads were filtered to remove the adapter contamination, and low-quality reads using TrimGalore!. Filtered reads were mapped to the reference genome using Bismark. MethylKit was used to identify differentially methylated regions (DMRs) (bases and tiles), showing statistically significant differential methylation between two groups: high and low-efficiency AMSCs. Hierarchical cluster analysis according to methylation patterns clearly defined groups with low and high cloning efficiency. We report 3704 bases with statistically significant differences in methylation and 10062 tiles with statistically significant differences in methylation. Most differentially methylated sites are intergenic 62%, 31% are intronic, 4% are located in exons and 4% in promoters. 37% of differentially methylated sites are located in known CpG islands (CGIs) and 4% in CpG island shores (CGSs).

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“…Aside from mice, the H3K4me3 barrier from donor somatic cells also exists in Xenopus , goats, and bovines and impedes the development of SCNT embryos ( Hörmanseder et al, 2017 ; Zhang et al, 2018c ; Deng et al, 2020 ; Zhou et al, 2020 ). However, based on transcriptome and epigenome analysis, H3K4me3 modification is not accounted for the failure of ZGA in pigs ( Liu et al, 2021 ). This result indicates that H3K4me3 as an epigenetic barrier may not be conserved in all mammals.…”

Section: Epigenetic Defects During Pre-implantation Development In Cl...mentioning

confidence: 99%

“…For example, KDM4D and KDM4E can rescue aberrant H3K9me3 deposition in bovine cloned embryos ( Liu et al, 2018a ). Injection of KDM4D or knockdown of SUV39H1/H2 can improve the development efficiency in pigs ( Weng et al, 2020 ; Liu et al, 2021 ). Moreover, two cloned monkeys were achieved successfully by injection of KDM4D in reconstructed embryos ( Liu et al, 2018b ; Liu et al, 2019 ).…”

Section: Strategies To Overcome Epigenetic Barriersmentioning

confidence: 99%

Epigenetic manipulation to improve mouse SCNT embryonic development

Sun

2022

Front. Genet.

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Cloned mammals can be achieved through somatic cell nuclear transfer (SCNT), which involves reprogramming of differentiated somatic cells into a totipotent state. However, low cloning efficiency hampers its application severely. Cloned embryos have the same DNA as donor somatic cells. Therefore, incomplete epigenetic reprogramming accounts for low development of cloned embryos. In this review, we describe recent epigenetic barriers in SCNT embryos and strategies to correct these epigenetic defects and avoid the occurrence of abnormalities in cloned animals.

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TDG is a pig-specific epigenetic regulator with insensitivity to H3K9 and H3K27 demethylation in nuclear transfer embryos

Cited by 16 publications

References 48 publications

Sperm‐borne proteins improve rabbit cloning efficiency via regulating embryonic cleavage and epigenetics

Sperm‐borne proteins improve rabbit cloning efficiency via regulating embryonic cleavage and epigenetics

Methylation genome wide profiling in lowly and highly efficient adipose somatic cell nuclear transfer in pigs

Epigenetic manipulation to improve mouse SCNT embryonic development

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