Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA252723 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1392390.fastq.gz | Fastqsanger.gz | |||
| SRR1392385.fastq.gz | Fastqsanger.gz | |||
| SRR1392386.fastq.gz | Fastqsanger.gz | |||
| SRR1392387.fastq.gz | Fastqsanger.gz | |||
| SRR1392388.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
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Project description:Canonical Wnt and Nodal signaling are both required for induction of the primitive streak (PS), which guides organization of the early embryo. The Wnt effector β-catenin is thought to function in these early lineage specification decisions via transcriptional activation of Nodal signaling. Here, we demonstrate a broader role for β-catenin in PS formation by analyzing its genome-wide binding in a human embryonic stem cell model of PS induction. β-catenin occupies regulatory regions in numerous PS and neural crest genes, and direct interactions between β-catenin and the Nodal effectors SMAD2/3 are required at these regions for PS gene activation. Furthermore, OCT4 binding in proximity to these sites is likewise required for PS induction, suggesting a collaborative interaction between β-catenin and OCT4. Induction of neural crest genes by β-catenin is repressed by SMAD2/3, ensuring proper lineage specification. This study provides mechanistic insight into how Wnt signaling controls early cell lineage decisions. Examination of β-catenin binding in hESC incubated in media control (RPMI), media containing CHIR or CHIR+SB for 6h and analyzed by ChIP-sequencing
2015-03-31 | E-GEOD-58476 | biostudies-arrayexpress
Project description:Canonical Wnt and Nodal signaling are both required for induction of the primitive streak (PS), which guides organization of the early embryo. The Wnt effector β-catenin is thought to function in these early lineage specification decisions via transcriptional activation of Nodal signaling. Here, we demonstrate a broader role for β-catenin in PS formation by analyzing its genome-wide binding in a human embryonic stem cell model of PS induction. β-catenin occupies regulatory regions in numerous PS and neural crest genes, and direct interactions between β-catenin and the Nodal effectors SMAD2/3 are required at these regions for PS gene activation. Furthermore, OCT4 binding in proximity to these sites is likewise required for PS induction, suggesting a collaborative interaction between β-catenin and OCT4. Induction of neural crest genes by β-catenin is repressed by SMAD2/3, ensuring proper lineage specification. This study provides mechanistic insight into how Wnt signaling controls early cell lineage decisions.
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Project description:The mechanism governing the transition of human embryonic stem cells towards differentiated cells is only partially understood. To explore this transition, the activity and expression of the ubiquitous phosphoinositide-3-kinase (PI3K α and β) were modulated. This study reports a pathway that dismantles the repression imposed by the EZH2 polycomb repressor on an essential stemness gene, NODAL, and on transcription factors required at differentiation to trigger primitive streak formation. The primitive streak is the site where gastrulation begins to give rise to the three embryonic cell layers from which all human tissues derive. The pathway involves an essential PI3Kβ-non-catalytic action for control of active-RAC1 levels, c-Jun-Nterminal-kinase activation and nuclear β-CATENIN accumulation. β-CATENIN deposition at promoters triggers the release of EZH2 repressor permitting both stemness maintenance (through control of NODAL) and correct differentiation, by allowing primitive streak master genes expression. PI3Kβ -mediated epigenetic control of EZH2/β-CATENIN might be modulated to direct stem cell differentiation.
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Project description:Gastrulation initiates when the epiblast differentiates into either definitive ectoderm or primitive streak. During the lineage bifurcation, the DNA dioxygenase TET1 plays dual roles in both transcriptional activation and repression, but how it exerts this bipartite control via 5-methylcytosine (5mC) oxidation-dependent and independent activities remains unclear. Here, we perform a monolayer differentiation of mouse embryonic stem cells (ESCs) into neuronal precursors to define at single-cell resolution how Tet1-/- cells undergo a lineage switch to primitive streak and subsequently form mesoderm and endoderm. We identify the Wnt repressor Tcf7l1 as a direct target of TET1 that controls a signaling cascade of Wnt/β-catenin upstream of Nodal. Disrupting the endogenous catalytic site of Tet1 in ESCs contributes to activation of Nodal and subsequently Wnt/β-catenin signaling, promoting tri-lineage differentiation into ectoderm, mesoderm and endoderm. Catalytically dead TET1 is sufficient in sustaining open neuroectoderm enhancers, by which gene expression is uncoupled from enhancer DNA demethylation, and indirectly keeping primitive streak enhancers inaccessible to Wnt regulators and effectors. DNA hypermethylation caused by TET1 catalytic dysfunction instead promotes precocious primitive streak gene activation when associated with CpG islands overlapping bivalent gene promotors. Moreover, hypermethylated regions amplify in numbers in the absence of TET1 through differentiation to affect genes associated with neurological functions. Our results reveal two-way safeguarding activities of TET1 separable by genomic features, where at CpG-poor distal enhancers TET1 maintains accessible chromatin permissive for neural fate independently of 5mC oxidation; at CpG-rich bivalent promoters it prevents premature gene activation inducing alternative fates by harnessing 5mC oxidation in Polycomb gene repression.
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