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Derivation of ground-state female ESCs maintaining gamete-derived DNA methylation

ABSTRACT: Derivation of ground-state female ESCs maintaining gamete-derived DNA methylation

PROVIDER: PRJNA328165 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR3749330_1.fastq.gz	Fastqsanger.gz
	SRR3749330_2.fastq.gz	Fastqsanger.gz
	SRR3749321_1.fastq.gz	Fastqsanger.gz
	SRR3749321_2.fastq.gz	Fastqsanger.gz
	SRR3749331_1.fastq.gz	Fastqsanger.gz

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Derivation of ground-state female ESCs maintaining gamete-derived DNA methylation

Project description:Inhibitors of MEK1/2 and Gsk3b, known as '2i' culture conditions, enhance the derivation of embryonic stem cells (ESCs) and promote ground-state pluripotency in rodents 1,2. Here we show that the derivation of female mouse ESCs in the presence of 2i (2i-ESCs) results in a widespread loss of DNA methylation including a massive erasure of genomic imprints. Despite this global loss of DNA methylation, the early-passage 2i-ESCs efficiently differentiate into somatic cells and this process requires genome-wide de novo DNA methylation. However, the majority of imprinting control regions (ICRs) remain unmethylated in the 2i-ESC-derived differentiated cells. Consistently, 2i-ESCs exhibit impairment of autonomous embryonic and placental development by tetraploid embryo complementation and nuclear transplantation. We identified the derivation conditions of female ESCs that display 2i-ESC-like transcriptional signatures while preserving gamete-derived DNA methylation and autonomous developmental potential. Upon prolonged culture, however, female ESCs exhibit ICR demethylation, regardless of culture conditions. Our results provide insights into derivation of female ESCs reminiscent of ICM of preimplantation embryos. S-ESCs are ESCs established under serum-containing medium. 2i_S_ESCs are ESCs established in 2i-containing medium, followed by maintenance in serum-containing medium.

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Derivation of ground-state female ESCs maintaining gamete-derived DNA methylation [gene expression]

Project description:Preimplantation embryos undergo a transient wave of genome-wide demethylation with the exception of imprinted genes that are critical for fetal development. Here we show that the derivation of female mouse embryonic stem cells (ESCs) in the presence of inhibitors of MEK1/2 and Gsk3 (2i-ESCs), known as ‘2i’ or “ground-state” culture conditions, results in a widespread loss of DNA methylation including a massive erasure of genomic imprints. In this study, we analyzed global gene expression profile and global DNA methylation status in 2i-ESCs and 2i-ESCs derived differentiated cells. S-ESCs are ESCs established under serum-containing medium. 2i_S_ESCs are ESCs established in 2i-containing medium, followed by maintenance in serum-containing medium.

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Derivation of ground-state female ESCs maintaining gamete-derived DNA methylation

Project description:This SuperSeries is composed of the SubSeries listed below.

2017-07-27 | GSE84165 | GEO

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Project description:Derivation of naive state of mouse embryonic stem cells (mESCs) in LIF+serum (LS) culture condition is strain dependent, whereas derivation of ground state mESCs is readily possible from all strains tested so far in “2i” culture condition. ESCs can be derived from the post-implantation stage mouse embryos (EpiSCs), showing primed characteristics. In the present study, we characterized and compared the transcriptional profile of naïve, primed and ground state mESCs. Considering the importance of genetic background of mouse model for ESCs derivation in conventional culture conditions, all ESCs lines used in the study were derived from the same strain of mice. We found distinct transcriptional profiles between naive, primed and ground state mESCs. Primed state mESCs exhibit lower expression of pluripotency markers along with higher expression of lineage specific markers compared to naive and ground state mESCs. We also demonstrate that the differentiation propensity of ESCs to specific germ layer varies depending on the pluripotency state of ESCs.

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