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Redox Heterogeneity in Mouse Embryonic Stem Cells Individualizes Cell Fate Decisions II

ABSTRACT: Redox Heterogeneity in Mouse Embryonic Stem Cells Individualizes Cell Fate Decisions II

PROVIDER: PRJNA1024539 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26297046_1.fastq.gz	Fastqsanger.gz
	SRR26297046_2.fastq.gz	Fastqsanger.gz
	SRR26297047_1.fastq.gz	Fastqsanger.gz
	SRR26297047_2.fastq.gz	Fastqsanger.gz
	SRR26297048_1.fastq.gz	Fastqsanger.gz

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Redox Heterogeneity in Mouse Embryonic Stem Cells Individualizes Cell Fate Decisions II

Project description:How cellular diversity is created is a key question in biology. Embryonic stem cells (ESCs) are pluripotent cells that can develop into any cell type in the body. Yet, the regulatory mechanisms that govern cell fate decisions remain largely unknown. Moreover, although genetically identical, individual ESCs are strikingly heterogeneous regarding their differentiation capacity but the molecular basis for this phenotypic heterogeneity is unclear. We now demonstrate that pluripotent mouse ESCs (mESCs) display large natural variations in mitochondrial reactive oxygen species (ROS) levels that individualize their nuclear redox state and redox-sensitive H3K4me3 landscape. By using intracellular redox probes, we sorted pluripotent and differentiating mESCs based on their nuclear redox environments into subpopulations and analysed their differentiation capacity. We show that more reduced mESCs are biased towards the mesendodermal fate and form the primitive streak upon differentiation. This mesendodermal specification is due to increased Wnt signaling pathway activity, mediated via a ROS-specific regulatory mechanism of p53-dependent expression of the Wnt ligand Wnt3, and increased H3K4me3 levels. We demonstrate that formation of a primitive streak-like structure by differentiating mESCs is initiated by increased mitochondrial ROS and p53 stabilization, followed by antioxidant Nrf2 response pathway activation that leads to a reduced nuclear redox environment, allowing for the accumulation of ROS-sensitive H3K4me3 marks and activation of Wnt3 and other mesendoderm-related gene expression. In summary, our study shows that natural variations in endogenous ROS levels individualize the H3K4me3 landscape of mESCs, and through gene expression changes govern their cell fate decision at the onset of gastrulation.

2024-07-07 | GSE244779 | GEO

Redox Heterogeneity in Mouse Embryonic Stem Cells Individualizes Cell Fate Decisions

Project description:Redox Heterogeneity in Mouse Embryonic Stem Cells Individualizes Cell Fate Decisions

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Redox Heterogeneity in Mouse Embryonic Stem Cells Individualizes Cell Fate Decisions I

Project description:Redox Heterogeneity in Mouse Embryonic Stem Cells Individualizes Cell Fate Decisions I

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Redox Heterogeneity in Mouse Embryonic Stem Cells Individualizes Cell Fate Decisions I

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In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions [microarray_dataset1]

Project description:The role of nutrient signaling processes in the fate decision of CD8 is incompletely understood. By performing in vivo pooled CRISPR-Cas9 screening, we uncovered nutrient signaling processes underpinning the dynamics and heterogeneity of CD8 T cell fate decisions.

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In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions [Pofut1_microarray]

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Redox Heterogeneity in Mouse Embryonic Stem Cells Individualizes Cell Fate Decisions

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

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In vivo CRISPR screening reveals nutrient signaling processes underpinning CD8+ T cell fate decisions [scRNA-seq]

Project description:The role of nutrient signaling processes in the fate decision of CD8 T cells are incompletely understood. By performing in vivo pooled CRISPR-Cas9 screening, we uncovered nutrient signaling processes underpinning the dynamics and heterogeneity of CD8 T cell fate decisions.

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