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Accession: PRJNA312762 ID: 312762

Mus musculus (house mouse)

Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells

See Genome Information for Mus musculus
Single-cell epigenome sequencing techniques have recently been developed. However, the combination of different layers of epigenome sequencing in an individual cell has not yet been achieved. Here, we developed a single-cell multi-omics sequencing technology (single-cell COOL-seq) that can analyze the chromatin state/nucleosome positioning, DNA methylation, copy number variation and ploidy simultaneously from the same individual mammalian cell. We used this method to analyze the reprogramming of the chromatin state and DNA methylation in mouse preimplantation embryos. We found that within < 12 h of fertilization, each individual cell undergoes global genome demethylation together with the rapid and global reprogramming of both maternal and paternal genomes to a highly opened chromatin state. This was followed by decreased openness after the late zygote stage. Furthermore, from the late zygote to the 4-cell stage, the residual DNA methylation is preferentially preserved on intergenic regions of the paternal alleles and intragenic regions of maternal alleles in each individual blastomere. However, chromatin accessibility is similar between paternal and maternal alleles in each individual cell from the late zygote to the blastocyst stage. The binding motifs of several pluripotency regulators are enriched at distal nucleosome depleted regions from as early as the 2-cell stage. This indicates that the cis-regulatory elements of such target genes have been primed to an open state from the 2-cell stage onward, long before pluripotency is eventually established in the ICM of the blastocyst. Genes may be classified into homogeneously open, homogeneously closed and divergent states based on the chromatin accessibility of their promoter regions among individual cells. This can be traced to step-wise transitions during preimplantation development. Our study offers the first single-cell and parental allele-specific analysis of the genome-scale chromatin state and DNA methylation dynamics at single-base resolution in early mouse embryos and provides new insights into the heterogeneous yet highly ordered features of epigenomic reprogramming during this process. Overall design: In total, we analyzed 24 single embryonic stem cells as well as 4 bulk samples of embryonic stem cells and 223 single cells from the oocyte stage to the blastocyst stage as well as 9 bulk samples of sperm cells.
AccessionPRJNA312762; GEO: GSE78140
ScopeMultiisolate
OrganismMus musculus[Taxonomy ID: 10090]
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus; Mus musculus
PublicationsGuo F et al., "Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells.", Cell Res, 2017 Aug;27(8):967-988
SubmissionRegistration date: 22-Feb-2016
Peking University
RelevanceModel Organism
Project Data:
Resource NameNumber
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Sequence data
SRA Experiments329
Publications
PubMed1
PMC1
Other datasets
BioSample329
GEO DataSets1
GEO Data Details
ParameterValue
Data volume, Supplementary Mbytes40419
SRA Data Details
ParameterValue
Data volume, Gbases2,040
Data volume, Tbytes1.01

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    Mus musculus
    Single-cell multi-omics sequencing of mouse early embryos and embryonic stem cells
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