Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages [RNA-seq and ChIP-seq]

ABSTRACT: The enteric nervous system (ENS) predominantly originates from vagal neural crest cells (VNC) that emerge from the caudal hindbrain, invade the foregut and populate the gastrointestinal tract. However, the gene regulatory network (GRN) orchestrating the early specification of VNC remains unknown. Using an EdnrB enhancer, we generated a comprehensive temporal map of the chromatin and transcriptional landscape of VNC in the avian model, revealing three VNC cell clusters (neural, neurogenic and mesenchymal), each predetermined epigenetically prior to neural tube delamination. We identify and functionally validate regulatory cores (Sox10/Tfap2B/SoxB/Hbox) mediating each programme and elucidate their combinatorial activities with other spatiotemporally-specific transcription factors (bHLH/NR). Our global deconstruction of the VNC-GRN in vivo sheds light on critical early regulatory mechanisms that may influence the divergent neural phenotypes in enteric neuropathies.

ORGANISM(S): Gallus gallus

PROVIDER: GSE131737 | GEO | 2019/11/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages

Project description:The enteric nervous system (ENS) predominantly originates from vagal neural crest cells (VNC) that emerge from the caudal hindbrain, invade the foregut and populate the gastrointestinal tract. However, the gene regulatory network (GRN) orchestrating the early specification of VNC remains unknown. Using an EdnrB enhancer, we generated a comprehensive temporal map of the chromatin and transcriptional landscape of VNC in the avian model, revealing three VNC cell clusters (neural, neurogenic and mesenchymal), each predetermined epigenetically prior to neural tube delamination. We identify and functionally validate regulatory cores (Sox10/Tfap2B/SoxB/Hbox) mediating each programme and elucidate their combinatorial activities with other spatiotemporally-specific transcription factors (bHLH/NR). Our global deconstruction of the VNC-GRN in vivo sheds light on critical early regulatory mechanisms that may influence the divergent neural phenotypes in enteric neuropathies.

2019-11-27 | GSE125711 | GEO

Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages

2019-11-27 | GSE125707 | GEO

Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages [scRNA-seq]

2019-11-27 | GSE137462 | GEO

Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages [CRISPR RNA-seq]

2019-11-27 | GSE125710 | GEO

Early shaping of the chromatin landscape specifies vagal neural crest into distinct lineages [RNA-seq]

Project description:Complex traits in enteropathies like Hirschsprung disease underscores a larger gene regulatory network (GRN) driving vagal neural crest (VNC) to form the enteric nervous system (ENS). To dissect the GRN and understand the function of non-coding regulatory regions, we used a novel highly conserved EdnrB E2 enhancer with a FoxD3 NC2 enhancer to generate a comprehensive map of VNC chromatin and transcriptional landscape during ENS development. Together with single-cell transcriptional profiles, we revealed three distinct lineages of VNC (glial, neuronal, and mesenchymal) that are each pre-specified by independent GRNs before delamination. We identified and functionally validated regulatory cores mediating the glial (Tfap2B and Sox10) and neuronal programmes (Sox3/Msx1) that in spatiotemporal combinations with other families of transcription factors, control the timing of enteric cell differentiation. Deconstructing the VNC-GRN identifies factors that pre-specifies cells to their presumptive fate and sheds light on how early GRN dysregulations influence the divergent neural phenotype in enteropathies.

2019-11-27 | GSE125709 | GEO

Reconstruction of the global neural crest gene regulatory network in vivo

Project description:Precise control of developmental processes is encoded in the genome in the form of gene regulatory networks (GRNs). Such multi-factorial systems are difficult to decode in vertebrates owing to their complex gene hierarchies and transient dynamic molecular interactions. Here we present a genome-wide in vivo reconstruction of the GRN underlying development of neural crest (NC), an emblematic embryonic multipotent cell population. By coupling NC-specific epigenomic and single-cell transcriptome profiling with genome/epigenome engineering in vivo, we identify multiple regulatory layers governing NC ontogeny, including NC-specific enhancers and super-enhancers, novel trans-factors and cis-signatures. Assembling the NC regulome has allowed the comprehensive reverse engineering of the NC-GRN at unprecedented resolution. Furthermore, identification and dissection of divergent upstream combinatorial regulatory codes has afforded new insights into opposing gene circuits t hat define canonical and neural NC fates. Our integrated approach, allowing dissection of cell-type-specific regulatory circuits in vivo, has broad implications for GRN discovery and investigation.

2019-10-09 | GSE121527 | GEO

Reconstruction of the global neural crest gene regulatory network in vivo [RNA-seq]

2019-10-09 | GSE130500 | GEO

Reconstruction of the global neural crest gene regulatory network in vivo [CRISPR_RNA-seq]

2019-10-09 | GSE121331 | GEO

Reconstruction of the global neural crest gene regulatory network in vivo [ChIP-seq]

2019-10-09 | GSE121329 | GEO