The connectome of neural crest enhancers reveals regulatory features of signaling systems
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA630814 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR11719963_1.fastq.gz | Fastqsanger.gz | |||
| SRR11719963_2.fastq.gz | Fastqsanger.gz | |||
| SRR11719964_1.fastq.gz | Fastqsanger.gz | |||
| SRR11719964_2.fastq.gz | Fastqsanger.gz | |||
| SRR11719965_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 44 |
Similar Datasets
Project description:The neural crest is a migratory stem cell population that gives rise to a wide array of cell types. The formation and differentiation of neural crest cells are controlled by a complex transcriptional network, which endows these cells with unique features such as multipotency and stemness. During migration, signaling systems modulate subcircuits within this network to ensure that neural crest cells differentiate at the right time and place. The wingless (Wnt) signaling pathway, in particular, plays an important role in defining developmental potential of these cells but, surprisingly few direct Wnt-target genes have been identified in the neural crest transcriptional network. To address this, we generated a high-resolution contact map of active enhancers in the neural crest and identified the direct targets of Wnt signaling in the neural crest genome via CUT&RUN for its nuclear effectors LEF1 and CTNNB1 (bCat).
2021-04-03 | GSE150006 | GEO
Project description:Cell fate commitment is controlled by cis-regulatory elements often located in remote regions of the genome. To examine the role of long-range DNA interactions in early development, we generated a high-resolution contact map of active enhancers in avian neural crest cells. This analysis uncovered a diverse repertoire of enhancers that are part of the gene regulatory network underlying specification. We found that neural crest identity is largely regulated by cis-regulatory elements that propagate signaling inputs to network components. These genomic sensors display a combination of optimal and suboptimal TCF/LEF-binding sites, which allow cells to respond to Wnt signaling in a position-dependent manner. We propose that, rather than acting as upstream activators, signaling systems feed into regulatory circuits in a hub-and-spoke architecture. These results shed light on the tridimensional organization of the neural crest genome and define how signaling systems provide progenitors with spatial cues that transform their molecular identity.
| S-EPMC8445387 | biostudies-literature
Project description:Enhancer connectome was studied in melanoma cell lines that express ALK ATI
2025-05-01 | GSE232300 | GEO
Project description:The BAF complex modulates chromatin accessibility. Specific BAF configurations have functional consequences, and subunit switches are essential for cell differentiation. ARID1B and its paralog ARID1A encode for mutually exclusive BAF subunits. De novo ARID1B haploinsufficient mutations cause a neurodevelopmental disorder spectrum, including Coffin-Siris syndrome, which is characterized by neurological and craniofacial features. Here, we reprogrammed ARID1B+/- Coffin-Siris patient-derived skin fibroblasts into iPSCs, and modeled cranial neural crest cell (CNCC) formation. We discovered that ARID1B is active only during the first stage of this process, coinciding with neuroectoderm specification, where it is part of a lineage-specific BAF configuration (ARID1B-BAF), including SMARCA4, and nine additional subunits. ARID1B-BAF acts as a gate-keeper, ensuring exit from pluripotency and lineage commitment, by attenuating NANOG, SOX2 and the thousands of enhancers directly regulated by these two pluripotency factors at the iPSC stage. In iPSCs, these enhancers are maintained active by an ARID1A-containing BAF. At the onset of differentiation, cells transition from ARID1A-BAF to ARID1B-BAF, eliciting attenuation of the NANOG/SOX2 networks, and triggering pluripotency exit. Coffin-Siris patient cells fail to perform the ARID1A/ARID1B switch, and maintain ARID1A-BAF at pluripotency enhancers throughout all stages of CNCC formation. This leads to a persistent and aberrant SOX2 and NANOG activity, which impairs CNCC formation. In fact, despite showing the typical neural crest signature (TFAP2A+, SOX9+), the ARID1B-haploinsufficient CNCCs are also NANOG-positive, in stark contrast with the ARID1B-wt CNCCs, which are NANOG-negative. These findings suggest a connection between ARID1B mutations, neuroectoderm formation, and a pathogenic mechanism for Coffin-Siris syndrome.
2021-10-12 | PXD028557 | Pride
Project description:Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed to pathogenic variants in the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD7 in neural crest development is well documented, how this factor is specifically upregulated in neural crest cells is not understood. Here, we use epigenomic profiling of chick and human neural crest to identify a cohort of enhancers regulating Chd7 expression in neural crest cells and other tissues. We functionally validate upstream transcription factor binding at candidate enhancers, revealing novel epistatic relationships between neural crest master regulators and Chd7, showing tissue-specific regulation of a globally-acting chromatin remodeller for the first time. Furthermore, we find conserved enhancer features in human embryonic epigenomic data and validate the activity of the human equivalent CHD7 enhancers in the chick embryo. Our findings embed Chd7 in the neural crest gene regulatory network and offer potentially clinically relevant elements for interpreting CHARGE syndrome cases without causative allocation.
2024-09-16 | GSE270155 | GEO
Project description:Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed topathogenic variantsin the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD743in neural crest development is well documented,how this factor is specifically upregulated in neural crest cells is not understood. Here, we use epigenomic profiling of chick and human neural crest to identify a cohort of enhancers regulating Chd7 expression in neural crest cells and other tissues. We functionally validate upstream transcription factor binding at candidate enhancers, revealing novel epistatic relationships between neural crest master regulators and Chd7, showing tissue-specific regulation of a globally-acting chromatin remodeller for the first time. Furthermore, we find conserved enhancer features in human embryonic epigenomic data and validate the activity of the human equivalent CHD7 enhancers in the chick embryo. Our findings embed Chd7 in the neural crest gene regulatory network and offer potentially clinically relevant elements for interpreting CHARGE syndrome cases without causative allocation.
2024-03-19 | GSE261486 | GEO
Project description:Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of molecular choices governing the emergence of neural crest heterogeneity from the ectoderm remains elusive. Gene regulatory networks govern these steps of embryonic development and cell specification towards definitive neural crest. Here, we combine ultra-dense single cell transcriptomes with machine-learning strategies and experimental validation to provide a comprehensive gene regulatory network driving vertebrate neural crest fate diversification, from induction to early migration stages. Transcription factor connectome and bifurcation analyses demonstrate emergence of early neural crest fates at the neural plate stage, alongside an unbiased multipotent neural crest lineage persisting until after epithelial-mesenchymal transition. We also define a new and transient neural border zone state, preceding choice between neural crest and placodes during gastrulation. Theis combination of experimental tests, with Machine Learning broadly applicable to single cell transcriptomics, deciphers the circuits driving cranial and vagal neural crest formation and provides a general model for investigating vertebrate GRNs in development, evolution and disease.
2024-03-29 | GSE198493 | GEO
Project description:Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of molecular choices governing the emergence of neural crest heterogeneity from the ectoderm remains elusive. Gene regulatory networks govern these steps of embryonic development and cell specification towards definitive neural crest. Here, we combine ultra-dense single cell transcriptomes with machine-learning strategies and experimental validation to provide a comprehensive gene regulatory network driving vertebrate neural crest fate diversification, from induction to early migration stages. Transcription factor connectome and bifurcation analyses demonstrate emergence of early neural crest fates at the neural plate stage, alongside an unbiased multipotent neural crest lineage persisting until after epithelial-mesenchymal transition. We also define a new and transient neural border zone state, preceding choice between neural crest and placodes during gastrulation. Theis combination of experimental tests, with Machine Learning broadly applicable to single cell transcriptomics, deciphers the circuits driving cranial and vagal neural crest formation and provides a general model for investigating vertebrate GRNs in development, evolution and disease.
2024-03-29 | GSE198492 | GEO
Project description:Neural crest cells exemplify cellular diversification from a multipotent progenitor population. However, the full sequence of molecular choices governing the emergence of neural crest heterogeneity from the ectoderm remains elusive. Gene regulatory networks govern these steps of embryonic development and cell specification towards definitive neural crest. Here, we combine ultra-dense single cell transcriptomes with machine-learning strategies and experimental validation to provide a comprehensive gene regulatory network driving vertebrate neural crest fate diversification, from induction to early migration stages. Transcription factor connectome and bifurcation analyses demonstrate emergence of early neural crest fates at the neural plate stage, alongside an unbiased multipotent neural crest lineage persisting until after epithelial-mesenchymal transition. We also define a new and transient neural border zone state, preceding choice between neural crest and placodes during gastrulation. Theis combination of experimental tests, with Machine Learning broadly applicable to single cell transcriptomics, deciphers the circuits driving cranial and vagal neural crest formation and provides a general model for investigating vertebrate GRNs in development, evolution and disease.
2024-03-29 | GSE198491 | GEO
Project description:Neurocristopathies such as CHARGE syndrome result from aberrant neural crest development. A large proportion of CHARGE cases are attributed topathogenic variantsin the gene encoding CHD7, chromodomain helicase DNA binding protein 7, which remodels chromatin. While the role for CHD743in neural crest development is well documented,how this factor is specifically upregulated in neural crest cells is not understood. Here, we use epigenomic profiling of chick and human neural crest to identify a cohort of enhancers regulating Chd7 expression in neural crest cells and other tissues. We functionally validate upstream transcription factor binding at candidate enhancers, revealing novel epistatic relationships between neural crest master regulators and Chd7, showing tissue-specific regulation of a globally-acting chromatin remodeller for the first time. Furthermore, we find conserved enhancer features in human embryonic epigenomic data and validate the activity of the human equivalent CHD7 enhancers in the chick embryo. Our findings embed Chd7 in the neural crest gene regulatory network and offer potentially clinically relevant elements for interpreting CHARGE syndrome cases without causative allocation.
2024-09-16 | GSE262042 | GEO