Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

ORGANISM(S): Gallus gallus

PROVIDER: GSE125709 | GEO | 2019/11/27

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

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

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 | GSE137462 | GEO

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

2019-11-27 | GSE125711 | GEO

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

2019-11-27 | GSE125710 | 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 [RNA-seq and ChIP-seq]

2019-11-27 | GSE131737 | GEO

Enteric glia express proteolipid protein 1 and are a transcriptionally unique population of glia in the mammalian nervous system

Project description:To identify the gene expression profile of enteric glia and assess the transcriptional similarity between enteric and extraenteric glia, we performed RNA sequencing analysis on PLP1-expressing cells in the mouse intestine. This analysis shows that enteric glia are transcriptionally unique and distinct from other cell types in the nervous system. Enteric glia express many genes characteristic of the myelinating glia, Schwann cells and oli- godendrocytes, although there is no evidence of myelination in the murine ENS. Total RNA expression profiles of PLP1 expressing enteric glial cells (GFP+) and non-glial cells (GFP-negative) were obtained from the ileum and colon of juvenile PLP1-eGFP transgenic mice.

2015-09-01 | E-GEOD-72560 | biostudies-arrayexpress

Ret loss-of-function decreases neural crest progenitor proliferation and restricts developmental fate potential during enteric nervous system development

Project description:The receptor tyrosine kinase gene RET plays a critical role in the fate specification of enteric neural crest cells (ENCCs) during enteric nervous system (ENS) development. Pathogenic RET loss of function (LoF) alleles are associated with Hirschsprung disease (HSCR), which is marked by aganglionosis of the gastrointestinal (GI) tract. ENCCs invade the developing GI tract, proliferate, migrate caudally, and differentiate into all of the major ENS cell types. Although the major phenotypic consequences, and the underlying transcriptional changes from Ret LoF in the developing ENS have been described, its cell type and state-specific effects are unknown. Consequently, we performed single-cell RNA sequencing (scRNA-seq) on an enriched population of ENCCs isolated from the developing GI tract of Ret null heterozygous and homozygous mouse embryos at embryonic day (E)12.5 and E14.5. We demonstrate four significant findings: (1) Ret-expressing ENCCs are a heterogeneous population composed of ENS progenitors as well as glial and neuronal committed cells; (2) neurons committed to a predominantly inhibitory motor neuron developmental trajectory are not produced under Ret LoF, leaving behind a mostly excitatory motor neuron developmental program; (3) HSCR-associated and Ret gene regulatory network genes exhibit distinct expression patterns across Ret-expressing ENCC cells with their expression impacted by Ret LoF; and (4) Ret deficiency leads to precocious differentiation and reduction in the number of proliferating ENS precursors. Our results support a model in which Ret contributes to multiple distinct cellular phenotypes and that Ret LoF contributes to GI aganglionosis in multiple independent ways.

2021-12-30 | GSE192676 | GEO

Expression data of mouse ENCCs and mouse embryonic Gut E14.5

Project description:Signaling of the RET receptor is crucial for the migration, proliferation, differentiation and survival of enteric neural crest cells (ENCCs) that form the enteric nervous system (ENS). Disturbances in RET signaling are associated with ENS defects, as is seen in patients with Hirschsprung disease. However, the downstream effectors of RET signalling in ENCCs is largely unknown. This study aims to gain new insight into the pathways involved in or triggered by RET in ENCCs. We used microarrays to detect the gene expression of mouse embryonic ENCCs when we stimulated with GDNF compare to control without GDNF and also compare to the gene expression of mouse embryonic gut (all are isolated from mouse embryonic day 14.5). Our aim is to gain insight of RET-GDNF downstream effectors and also all signalling pathways that regulate by RET-GDNF in ENCCs during development.

2011-12-07 | GSE34208 | GEO

Loss of enteric neuronal Ndrg4 promotes colorectal cancer via increased release of Nid1 and Fbln2

Project description:The N-Myc Downstream-Regulated Gene 4 (NDRG4), a prominent biomarker for colorectal cancer (CRC), is specifically expressed by enteric neurons. Considering that nerves are important members of the tumor microenvironment, we here establish different Ndrg4 knockout (Ndrg4-/-) CRC models and an in-direct co-culture of primary enteric nervous system (ENS) cells and intestinal organoids to identify whether the ENS, via NDRG4, affects intestinal tumorigenesis. Linking immunostainings and gastrointestinal motility (GI) assays, we show that absence of Ndrg4 does not trigger any functional or morphological GI-abnormalities. However, combining in vivo, in vitro and quantitative proteomics data, we uncover that Ndrg4 knockdown is associated with enlarged intestinal adenoma development and that organoid growth is boosted by the Ndrg4-/- ENS cell secretome, which is enriched for Nidogen-1 (Nid1) and Fibulin-2 (Fbln2). Moreover, NID1 and FBLN2 are expressed in enteric neurons, enhance tumorigenic capacities of CRC cells and are enriched in human CRC secretomes. Hence, we provide evidence that the ENS, via loss of Ndrg4, is involved in colorectal pathogenesis and that ENS-derived Nidogen-1 and Fibulin-2 enhance colorectal carcinogenesis.

2021-04-23 | PXD024502 | Pride

Glial Guidance Drives Postnatal Intestinal Reinnervation by Enteric Neurons

Project description:This study investigates the phenomenon of postnatal plasticity within the enteric nervous system (ENS), specifically investigating the reinnervation potential of post-mitotic enteric neurons. Employing BAF53b-Cre for selective tracing, the reinnervation capabilities of postnatal enteric neurons in multiple model systems are shown. Denervated enteric neurons exhibit the ability to regenerate neurites in vitro, with neurite complexity and direction notably influenced by contact with enteric glial cells (EGCs). In vivo nerve fibers from transplanted enteric neurons exclusively interface with EGCs. Resident EGCs are sustained after Cre dependent ablation of enteric neurons and govern the architecture of the ENS by reinnervating enteric neurons. Transplantation experiments underscore the swift reintegration and reinnervation potential of post-mitotic neurons, leading to restored muscle function within two weeks. Optogenetic investigations further delineate time-dependent functional recovery via transplantation of isolated enteric ganglia. These revelations demonstrate the structural and functional reinnervation capacity of post-mitotic enteric neurons, underscored by EGC guidance.

2024-07-16 | GSE242208 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data