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1.
Cell Rep ; 42(2): 112100, 2023 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-36763500

RESUMO

During pre-implantation stages of mammalian development, maternally stored material promotes both the erasure of the sperm and oocyte epigenetic profiles and is responsible for concomitant genome activation. Here, we have utilized single-cell methylome and transcriptome sequencing (scM&T-seq) to quantify both mRNA expression and DNA methylation in oocytes and a developmental series of human embryos at single-cell resolution. We fully characterize embryonic genome activation and maternal transcript degradation and map key epigenetic reprogramming events in developmentally high-quality embryos. By comparing these signatures with early embryos that have undergone spontaneous cleavage-stage arrest, as determined by time-lapse imaging, we identify embryos that fail to appropriately activate their genomes or undergo epigenetic reprogramming. Our results indicate that a failure to successfully accomplish these essential milestones impedes the developmental potential of pre-implantation embryos and is likely to have important implications, similar to aneuploidy, for the success of assisted reproductive cycles.


Assuntos
Multiômica , Sêmen , Animais , Humanos , Masculino , Desenvolvimento Embrionário/genética , Embrião de Mamíferos/metabolismo , Oócitos/metabolismo , Epigênese Genética , Blastocisto/metabolismo , Mamíferos
2.
PLoS Genet ; 12(11): e1006427, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27835649

RESUMO

Thousands of regions in gametes have opposing methylation profiles that are largely resolved during the post-fertilization epigenetic reprogramming. However some specific sequences associated with imprinted loci survive this demethylation process. Here we present the data describing the fate of germline-derived methylation in humans. With the exception of a few known paternally methylated germline differentially methylated regions (DMRs) associated with known imprinted domains, we demonstrate that sperm-derived methylation is reprogrammed by the blastocyst stage of development. In contrast a large number of oocyte-derived methylation differences survive to the blastocyst stage and uniquely persist as transiently methylated DMRs only in the placenta. Furthermore, we demonstrate that this phenomenon is exclusive to primates, since no placenta-specific maternal methylation was observed in mouse. Utilizing single cell RNA-seq datasets from human preimplantation embryos we show that following embryonic genome activation the maternally methylated transient DMRs can orchestrate imprinted expression. However despite showing widespread imprinted expression of genes in placenta, allele-specific transcriptional profiling revealed that not all placenta-specific DMRs coordinate imprinted expression and that this maternal methylation may be absent in a minority of samples, suggestive of polymorphic imprinted methylation.


Assuntos
Metilação de DNA/genética , Impressão Genômica/genética , Células Germinativas/metabolismo , Oócitos/metabolismo , Animais , Blastocisto/metabolismo , Ilhas de CpG/genética , Feminino , Humanos , Masculino , Camundongos , Placenta/metabolismo , Gravidez , Primatas/genética , Primatas/crescimento & desenvolvimento , Espermatozoides/metabolismo
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