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Series GSE139984 Query DataSets for GSE139984
Status Public on Feb 13, 2020
Title Strand-specific single-cell methylomics reveals distinct modes of DNA demethylation dynamics in preimplantation mouse and human embryos
Organisms Homo sapiens; Mus musculus
Experiment type Methylation profiling by high throughput sequencing
Summary DNA methylation (5mC) is central to cellular identity and the global erasure of 5mC from the parental genomes during preimplantation mammalian development. This process is critical to reset the methylome of terminally differentiated gametes to the become pluripotent cells in the blastocyst. While active and passive modes of demethylation have both been suggested to play a role in this process, the relative contribution of these two mechanisms to genome-wide 5mC erasure remains unclear. Here, we report a new high-throughput single-cell method (scMspJI-seq) that enables strand-specific quantification of 5mC, thereby allowing us to systematically probe the dynamics of global demethylation. First, when applied to hybrid mouse embryonic stem cells, we identified substantial cell-to-cell strand-specific 5mC heterogeneity with a small group of cells displaying asymmetric levels of 5mCpG between the two DNA strands of a chromosome and suggesting loss of maintenance methylation. Next, using scMspJI-seq in preimplantation mouse development, we discovered that maintenance methylation is active till the 16-cell stage followed by passive demethylation in a fraction of cells within 2 the early blastocyst at the 32-cell stage of development. Finally, we found that human preimplantation embryos qualitatively show slower yet similar demethylation dynamics as mouse preimplantation embryos. Collectively, these results demonstrate that scMspJI-seq is a sensitive and cost effective method to map the strand-specific genome- wide patterns of 5mC in single cells, thereby enabling quantitative investigation of methylation dynamics in developmental systems.
Overall design 72 libraries
Contributor(s) Sen M, Mooijman D, Boisset J, Chialastri A, Popovic M, Heindryckx B, Chuva de Sousa Lopes S, Dey SS, van Oudenaarden A
Citation(s) 33627650
Submission date Nov 05, 2019
Last update date Mar 16, 2021
Contact name Maya Sen
Organization name Hubrecht Institute
Street address 8 Uppsalalaan
City Utrecht
ZIP/Postal code 3584CT
Country Netherlands
Platforms (3)
GPL16417 Illumina MiSeq (Mus musculus)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL19057 Illumina NextSeq 500 (Mus musculus)
Samples (62)
GSM4151085 E14 DNMT1 KO- Library 1
GSM4151086 E14 DNMT1 KO single cells- Library 2
GSM4151087 E14 DNMT1 KO single cells- Library 3
BioProject PRJNA587784
SRA SRP228613

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Supplementary file Size Download File type/resource
GSE139984_RAW.tar 380.4 Mb (http)(custom) TAR (of TXT)
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Raw data are available in SRA
Processed data provided as supplementary file

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