Ontology highlight
ABSTRACT:
PROVIDER: PRJNA445633 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:SCNT embryos are defective for H3K27me3 imprinting
| PRJNA448159 | ENA
Project description:SCNT embryos are defective for H3K27me3 imprinting [ChIP-seq]
| PRJNA470928 | ENA
Project description:SCNT embryos are defective for H3K27me3 imprinting [RNA-seq]
| PRJNA430154 | ENA
Project description:Animal cloning can be achieved through somatic cell nuclear transfer (SCNT), yet the success rate is very low. Recent studies have revealed H3K9me3 in donor cells and abnormal Xist activation as epigenetic barriers that impede SCNT reprogramming. Here we overcome both barriers by using Xist knockout donor cells combined with overexpressing Kdm4d and achieved the highest cloning efficiency in mice. However, post-implantation developmental defects and abnormal placenta were still observed, indicating presence of additional epigenetic barriers impedes SCNT cloning. Comparative DNA methylome analysis of IVF and SCNT blastocysts identified many abnormally methylated regions in SCNT embryos, despite successful global methylome reprogramming. Strikingly, allelic transcriptome and ChIP-seq analyses of preimplantation SCNT embryos revealed a complete loss of H3K27me3 imprinting, which likely accounts for postimplantation developmental defects of SCNT embryos. This study not only provides an efficient method for mouse cloning, but also paves the way for further improving SCNT cloning efficiency.
2018-06-27 | GSE114307 | GEO
Project description:Animal cloning can be achieved through somatic cell nuclear transfer (SCNT), yet the success rate remains very low. Recent studies have revealed two epigenetic barriers, H3K9me3 in donor cells and abnormal Xist activation, that impede SCNT reprogramming. Here we overcome both barriers by combining the use of Xist knockout donor cells and overexpressing Kdm4d, which allowed us to achieve the highest mouse cloning efficiency. However, SCNT-associated developmental defects and abnormal placenta were still observed, suggesting the existence of additional epigenetic defects in these SCNT embryos. Comparative DNA methylome analysis of IVF and SCNT blastocysts identified many abnormally methylated regions in SCNT embryos, despite successful global methylome reprogramming. Strikingly, allelic transcriptome analyses of SCNT blastocysts revealed a complete loss-of-imprinting at the H3K27me3-dependent imprinted genes, which may account for postimplantation developmental defects of SCNT embryos. This study thus not only provides the most efficient method for mouse cloning but also points the way for further improve SCNT cloning.
2018-06-27 | GSE109214 | GEO
Project description:Animal cloning can be achieved through somatic cell nuclear transfer (SCNT), yet the success rate remains very low. Recent studies have revealed two epigenetic barriers, H3K9me3 in donor cells and abnormal Xist activation, that impede SCNT reprogramming. Here we overcome both barriers by combining the use of Xist knockout donor cells and overexpressing Kdm4d, which allowed us to achieve the highest mouse cloning efficiency. However, SCNT-associated developmental defects and abnormal placenta were still observed, suggesting the existence of additional epigenetic defects in these SCNT embryos. Comparative DNA methylome analysis of IVF and SCNT blastocysts identified many abnormally methylated regions in SCNT embryos, despite successful global methylome reprogramming. Strikingly, allelic transcriptome analyses of SCNT blastocysts revealed a complete loss-of-imprinting at the H3K27me3-dependent imprinted genes, which may account for postimplantation developmental defects of SCNT embryos. This study thus not only provides the most efficient method for mouse cloning but also points the way for further improve SCNT cloning.
2018-06-27 | GSE112528 | GEO
Project description:Pig cloning by somatic cell nuclear transfer (SCNT) frequently undergoes incomplete epigenetic remodeling during the maternal-to-zygotic transition, which leads to a significant embryonic loss before implantation. Here, we generated the first genome-wide landscapes of histone methylation in pig SCNT embryos. Excessive H3K9me3 and H3K27me3, but not H3K4me3, were observed in the genomic regions with unfaithful embryonic genome activation and donor cell-specific gene silencing. A combination of H3K9 demethylase KDM4A and GSK126, an inhibitor of H3K27me3 writer, could remove these epigenetic barriers and restore the global transcriptome in SCNT embryos. More importantly, TDG was defined as a pig-specific epigenetic regulator for nuclear reprogramming, which was not reactivated by H3K9me3 and H3K27me3 removal. Both combined treatment and transient TDG overexpression could promote DNA demethylation and enhance the blastocyst forming rates of SCNT embryos, which offers valuable methods to increase the cloning efficiency of genome-edited pigs for agricultural and biomedical purposes.
2021-09-21 | GSE161525 | GEO
Project description:Somatic cell nuclear transfer (SCNT) can be used to reprogram differentiated somatic cells to a totipotent state but has poor efficiency in supporting full-term development. H3K9me3 is considered to be an epigenetic barrier to zygotic genomic activation in 2-cell SCNT embryos. However, the mechanism underlying the failure of H3K9me3 reprogramming during SCNT embryo development remains elusive. Here, we perform genome-wide profiling of H3K9me3 in cumulus cell-derived SCNT embryos. We find redundant H3K9me3 marks are closely related to defective minor zygotic genome activation. Moreover, SCNT blastocysts show severely indistinct lineage-specific H3K9me3 deposition. We identify MAX and MCRS1 as potential H3K9me3-related transcription factors and are essential for early embryogenesis. Overexpression of Max and Mcrs1 significantly benefits SCNT embryo development. Notably, MCRS1 partially rescues lineage-specific H3K9me3 allocation, and further improves the efficiency of full-term development. Importantly, our data confirm the conservation of deficient H3K9me3 differentiation in Sertoli cell-derived SCNT embryos, which may be regulated by alternative mechanisms.
2023-07-10 | GSE194341 | GEO
Project description:Somatic cell nuclear transfer (SCNT) can be used to reprogram differentiated somatic cells to a totipotent state but has poor efficiency in supporting full-term development. H3K9me3 is considered to be an epigenetic barrier to zygotic genomic activation in 2-cell SCNT embryos. However, the mechanism underlying the failure of H3K9me3 reprogramming during SCNT embryo development remains elusive. Here, we perform genome-wide profiling of H3K9me3 in cumulus cell-derived SCNT embryos. We find redundant H3K9me3 marks are closely related to defective minor zygotic genome activation. Moreover, SCNT blastocysts show severely indistinct lineage-specific H3K9me3 deposition. We identify MAX and MCRS1 as potential H3K9me3-related transcription factors and are essential for early embryogenesis. Overexpression of Max and Mcrs1 significantly benefits SCNT embryo development. Notably, MCRS1 partially rescues lineage-specific H3K9me3 allocation, and further improves the efficiency of full-term development. Importantly, our data confirm the conservation of deficient H3K9me3 differentiation in Sertoli cell-derived SCNT embryos, which may be regulated by alternative mechanisms.
2023-07-10 | GSE194327 | GEO
Project description:As a histone hallmark for transcription repression, Histone H3 lysine 27 trimethylation (H3K27me3) plays important roles in mammalian embryo development and induced pluripotent stem cells (iPSCs) generation. However, the expression profile and roles of H3K27me3 in bovine somatic cell nuclear transfer (SCNT) reprogramming remain poorly understood. In this study, we find SCNT embryos exhibit global hypermethylation of H3K27me3 from two-cell to eight-cell stage and its removal by ectopically expressed H3K27me3 demethylase-KDM6A could greatly improves SCNT efficiency. To illuminate the mechanism of improving SCNT reprogramming efficiency of KDM6A overexpression, we performed RNA sequencing of transcripts in SCNT morula with or without KDM6A overexpression. RNA-seq reveal that KDM6A overexpression could enhance transcription of genes mainly involved cell adhesion and cellular metabolism process, as well as X-linked genes. We first provides the transcriptome data of bovine SCNT morula with or without KDM6A overexpression. Meanwhile, we compared the differences of transcriptome between SCNT eight-cell embryos and morula. Our study provide a more promising approach to improving the efficiency of SCNT reprogramming and contribute to understanding the mechanism of first cell fate determine during embryo development in bovine.
2019-01-31 | GSE114596 | GEO