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Age-dependent replacement of neural-crest derived enteric neurons by a novel mesodermal lineage and its functional consequences

ABSTRACT: Age-dependent replacement of neural-crest derived enteric neurons by a novel mesodermal lineage and its functional consequences

PROVIDER: PRJNA656839 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12441050_1.fastq.gz	Fastqsanger.gz
	SRR12441050_2.fastq.gz	Fastqsanger.gz
	SRR12441051_1.fastq.gz	Fastqsanger.gz
	SRR12441051_2.fastq.gz	Fastqsanger.gz
	SRR12441052_1.fastq.gz	Fastqsanger.gz

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Age-dependent replacement of neural-crest derived enteric neurons by a novel mesodermal lineage and its functional consequences

Project description:During fetal development, neural crest precursors give rise to neurons of the enteric nervoussystem (ENS). However, given our evolving understanding of the dynamic nature of the ENS, itis not clear whether this developmental paradigm holds true at different post-natal stages. Here,we show that due to loss of GDNF-RET signaling with age, neural crest-derived neurons un-dergo a progressive decline in numbers. They are replaced by neurons derived from the embry-onic mesoderm which, with increasing age, become the dominant form of neurons in the ENS,and this is associated with functional deficits in intestinal motility. Using single cell transcrip-tomics and immunochemical approaches, we characterize these mesoderm-derived neuronsand show that this novel lineage of neurons expresses MET and is dependent on HGF for itsexpansion. Normal intestinal function in the adult gastrointestinal tract therefore appears to re-quire an optimal balance between these two distinct lineages within the ENS.

2021-04-30 | GSE156146 | GEO

Characterization and transplantation of enteric neural crest cells from human induced pluripotent stem cells

Project description:Here, human pluripotent stem cells (hiPSCs and hESCs) were induced to differentiate to enteric neurons through neural crest specification. We sequenced mRNA samples from enteric neuronal differentiation of human pluripotent stem cells at 4 different stage to generate the gene expression profiles of these cells.

2017-06-14 | GSE79928 | GEO

Enteric neural crest-derived cells at the invasive wavefront are transcriptionally distinct

Project description:Enteric nervous system (ENS) development relies on intestinal colonization by enteric neural crest-derived cells (ENCDCs). This is driven by a population of highly migratory and proliferative cells at the wavefront, but the unique molecular characteristics of the wavefront are unknown. ENCDCs from the wavefront and the trailing region proximal were isolated from 11.5 days post coitum (dpc) Wnt1-tdT mouse intestine and subjected to RNA-seq. Wavefront ENCDCs were transcriptionally distinct from trailing ENCDCs, and temporal modelling confirmed their relative immaturity. Wavefront ENCDCs exhibited altered expression of ECM and cytoskeletal genes, consistent with a migratory phenotype. Unlike postnatal enteric neural stem cells, wavefront ENCDCs possessed characteristics of cells undergoing epithelial-mesenchymal transition and lacked neuronal or glial commitment.

2023-02-15 | GSE217757 | GEO

Expression data from embryonic day 17 (E17) enteric neural crest-dervied cells (ENCDC) and non-ENCDC

Project description:During the later stages of enteric nervous system (ENS) development, enteric neural crest derived cells (ENCDC) that have colonized the bowel must complete differentiating and mature into neurons and glia. This process is controlled by a complex array of intrinsic and extrinsic factors. We used microarrays to dermine which genes were differntially expressed in ENCDC versus other cells in the developing bowel. We identified many geness enriched in ENCDC with potential roles in the later stages of ENS development

2018-10-09 | GSE120936 | GEO

Single-cell profiling coupled with lineage analysis reveals vagal and sacral neural crest contributions to the developing enteric nervous system

Project description:During development, much of the enteric nervous system (ENS) arises from the vagal neural crest that emerges from the caudal hindbrain and colonizes the entire gastrointestinal tract. However, a second contribution to the ENS comes from the sacral neural crest that arises in the caudal neural tube and populates the post-umbilical gut. By coupling single cell transcriptomics with axial-level specific lineage tracing in avian embryos, we compared the contributions of embryonic vagal and sacral neural crest cells to the pre-umbilical and post-umbilical chick ENS and the associated peripheral ganglia (the Nerve of Remak and pelvic plexuses) at embryonic day (E) 10.

2023-10-23 | GSE242228 | GEO

Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor

Project description:Early anteroposterior regionalisation of human neural crest is shaped by a pro-mesodermal factor

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Early anteroposterior regionalization of human neural crest is shaped by a pro-mesodermal factor

Project description:Early anteroposterior regionalization of human neural crest is shaped by a pro-mesodermal factor

| PRJNA763606 | ENA

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

Enteric neural crest-derived cells at the invasive wavefront are transcriptionally distinct

Project description:Enteric neural crest-derived cells at the invasive wavefront are transcriptionally distinct

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Avian ceca are required for hindgut enteric nervous system development by promoting enteric neural crest cell proliferation and inhibiting neuronal differentiation via non-canonical Wnt signaling

Project description:The enteric nervous system (ENS), which is derived from enteric neural crest cells (ENCCs) during gut development, represents the neuronal innervation of the gastrointestinal tract and is critical for regulating normal intestinal function. Compromised ENCC migration can lead to Hirschsprung Disease, which is characterized by an aganglionic distal bowel. We find that removal of the ceca, a paired structure present at the midgut-hindgut junction in avian intestine, leads to severe hindgut aganglionosis, suggesting that the ceca are required for ENS development. To test this, we replaced the ceca of embryonic day 6 (E6) wild-type chicks with ceca from transgenic GFP chicks. Interestingly, the entire hindgut ENS arises from the GFP+ ceca-derived ENCC population. Comparative transcriptome profiling of the cecal buds compared to the interceca region shows that the non-canonical Wnt signaling pathway is preferentially expressed within the ceca. Specifically, Wnt11 is highly expressed in the ceca, as confirmed by RNA in situ hybridization, leading us to hypothesize that cecal expression of Wnt11 is important for ENCC colonization of the hindgut. Organ cultures were prepared using E6 avian intestine, when ENCCs are migrating through the ceca, and showed that Wnt11 inhibits enteric neuronal differentiation. These results reveal an essential role for the ceca during hindgut ENS formation and highlight an important function for non-canonical Wnt signaling in regulating ENCC differentiation and thereby promoting their migration into the colon.

2021-11-01 | GSE182783 | GEO

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