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Status |
Public on Nov 27, 2019 |
Title |
Early shaping of the chromatin landscape specifies vagal neural crest into distinct lineages [RNA-seq] |
Organism |
Gallus gallus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
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.
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Overall design |
Transcriptomic profilling of avian neural crest cells isolated from their in vivo context at HH12, HH18 and HH25
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Contributor(s) |
Ling I, Sauka-Spengler T |
Citation(s) |
31792380, 33111104 |
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Submission date |
Jan 27, 2019 |
Last update date |
Nov 02, 2020 |
Contact name |
Tatjana Sauka-Spengler |
E-mail(s) |
tatjana.sauka-spengler@imm.ox.ac.uk
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Organization name |
MRC Weatherall Institute of Molecular Medicine
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Department |
University of Oxford
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Lab |
Sauka-Spengler lab
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Street address |
Radcliffe Department of Medicine
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City |
Oxford |
State/province |
Oxfordshire |
ZIP/Postal code |
OX3 9DS |
Country |
United Kingdom |
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Platforms (1) |
GPL19787 |
Illumina NextSeq 500 (Gallus gallus) |
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Samples (16)
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This SubSeries is part of SuperSeries: |
GSE125711 |
Early chromatin shaping predetermines multipotent vagal neural crest into neural, neuronal and mesenchymal lineages |
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Relations |
BioProject |
PRJNA517322 |
SRA |
SRP182591 |