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Cell fate roadmap with pre-implantation lineage signatures during primed-to-naive transition process

ABSTRACT: Cell fate roadmap with pre-implantation lineage signatures during primed-to-naive transition process

PROVIDER: PRJNA728461 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14476369_1.fastq.gz	Fastqsanger.gz
	SRR14476369_2.fastq.gz	Fastqsanger.gz
	SRR14476370_1.fastq.gz	Fastqsanger.gz
	SRR14476370_2.fastq.gz	Fastqsanger.gz
	SRR14476371_1.fastq.gz	Fastqsanger.gz

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Cell fate roadmap with pre-implantation lineage signatures during primed-to-naive transition process

Project description:We describe the global cell roadmap during primed-to-naive transition process in single-cell level by performing integrated scRNA-seq analysis between primed, day 6, day 8, day 10, day14 and naïve (10× genomics)scRNA-seq libraries generated in this study.

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A rewiring of DNA replication mediated by MRE11 exonuclease underlies primed-to-naive cell de-differentiation

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Project description:Cell fate roadmap of human primed-to-naive transition reveals preimplantation cell lineage signatures

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Naive Pluripotent Stem Cells Display Transcriptional and Epigenetic Signatures of the Human Pre-Implantation Embryo

Project description:Significant interest has been devoted to the isolation of human pluripotent stem cells displaying the naive state of mouse embryonic stem cells. However, to what extent naive human cells isolated in culture resemble pluripotent cells in vivo remains unclear. Here we present three lines of evidence indicating that naive pluripotent stem cells generated in the absence of transgenes share defining molecular signatures with the human pre-implantation embryo. First, a comprehensive analysis of the transposcriptome reveals that naive human cells have a retroelement expression profile of human cleavage stage embryos. Second, base-resolution mapping of the DNA methylome in naive human cells reveals a genome-wide reduction in CpG and non-CpG methylation levels. Third, female naive cells exhibit an X chromosome status that is similar to that of the human blastocyst. Our work demonstrates that pluripotent stem cells with epigenomic hallmarks of the early human embryo can be directly captured in vitro. Examine the methylomes of 6 naÃ¯ve, 2 primed and 2 re-primed human embryonic stem cells

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Project description:Pluripotent stem cells can give rise to the three embryonic germ layers and the characterization of their properties is crucial to exploit their therapeutic potential. Mouse embryonic stem cells (mESCs) are isolated and usually maintained in vitro in a primed state that resembles the post-implantation epiblast features. Furthermore, primed mESCs can be de-differentiated to a naive state that resembles the pre-implantation inner cell mass (ICM). Cell differentiation or genotoxic stress, among others, can alter DNA replication, which is a flexible process able to adapt to different cellular contexts. Here, we demonstrate that primed-to-naive mESC reprogramming triggers replication fork slowdown, increased fork asymmetry and a compensatory activation of dormant origins. Using iPOND (“isolation of proteins on nascent DNA”) coupled to mass spectrometry we have characterized the changes in replisome composition between naive and primed mESCs. Several DNA repair factors, including MRE11 nuclease, are enriched in naive mESCs forks, while factors involved in ubiquitin-dependent protein metabolism are enriched in primed mESC forks. We report that primed-to-naive mESC de-differentiation promotes recruitment of MRE11 to the forks in response to transcription-replication conflicts, underlying the DNA replication rewiring required for efficient mESC reprogramming.

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