Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA390776 | ENA |
REPOSITORIES: ENA
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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
Project description:Epigenetic regulatory mechanisms are underappreciated but critical for enteric nervous system (ENS) development and maintenance. We discovered that fetal loss of the epigenetic regulator Bap1 in the ENS lineage causes severe postnatal bowel dysfunction and early death in Tyrosinase-Cre; Bap1fl/fl mice. Bap1-depleted ENS appears normal in neonates, however, by postnatal day 15 (P15), Bap1-deficient enteric neurons are largely absent from the small and large intestine of Tyrosinase-Cre; Bap1fl/fl mice. Bowel motility becomes markedly abnormal with disproportionate loss of cholinergic neurons. Single-cell RNA sequencing at P5 shows that fetal Bap1 loss inTyrosinase-Cre; Bap1fl/fl mice markedly alters the composition and relative proportions of enteric neuron subtypes. In contrast, postnatal deletion of Bap1 did not cause enteric neuron loss or impaired bowel motility. These findings suggest that BAP1 is critical for postnatal enteric neuron differentiation and for enteric neuron survival.
2024-04-01 | GSE242001 | GEO
Project description:The enteric nervous system (ENS) is an essential network of neurons and glia in the bowel wall. Defects in ENS development can result in Hirschsprung disease (HSCR), a life-threatening condition characterized by severe constipation, abdominal distention, bilious vomiting, and failure to thrive. A growing body of literature connects HSCR to alterations in miRNA expression, but there are limited data on the normal miRNA landscape in the developing ENS. We sequenced small RNAs (smRNA-seq) and messenger RNAs (mRNA-seq) in ENS precursors of mid-gestation Ednrb-EGFP mice and compared them to aggregated RNA from all other cells in the developing bowel. Our smRNA-seq results identified 73 miRNAs that were significantly enriched and highly expressed in the developing ENS, with miR-9, miR-27b, miR-124, miR-137, and miR-488 as our top 5 miRNAs that are conserved in humans. However, contrary to prior reports, our follow-up analyses of miR-137 showed that loss of Mir137 in Nestin-cre, Wnt1-cre, Sox10-cre, or Baf53b-cre lineage cells had no effect on mouse survival or ENS development. Our data provide important context for future studies of miRNA in HSCR and other ENS diseases and highlight open questions about facility-specific factors in development.
2023-12-26 | GSE250527 | GEO
Project description:The enteric nervous system (ENS) is an essential network of neurons and glia in the bowel wall. Defects in ENS development can result in Hirschsprung disease (HSCR), a life-threatening condition characterized by severe constipation, abdominal distention, bilious vomiting, and failure to thrive. A growing body of literature connects HSCR to alterations in miRNA expression, but there are limited data on the normal miRNA landscape in the developing ENS. We sequenced small RNAs (smRNA-seq) and messenger RNAs (mRNA-seq) in ENS precursors of mid-gestation Ednrb-EGFP mice and compared them to aggregated RNA from all other cells in the developing bowel. Our smRNA-seq results identified 73 miRNAs that were significantly enriched and highly expressed in the developing ENS, with miR-9, miR-27b, miR-124, miR-137, and miR-488 as our top 5 miRNAs that are conserved in humans. However, contrary to prior reports, our follow-up analyses of miR-137 showed that loss of Mir137 in Nestin-cre, Wnt1-cre, Sox10-cre, or Baf53b-cre lineage cells had no effect on mouse survival or ENS development. Our data provide important context for future studies of miRNA in HSCR and other ENS diseases and highlight open questions about facility-specific factors in development.
2023-12-26 | GSE250526 | GEO
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
Project description:The enteric nervous system (ENS) is contained within two layers of the gut wall and is made up of neurons, immune cells, and enteric glia cells (EGCs) that regulate gastrointestinal (GI) function. EGCs in both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) change in response to inflammation, referred to as reactive gliosis. Whether EGCs restricted to a specific layer or region within the GI tract alone can influence intestinal immune response is unknown. Using bulk RNA-sequencing and in situ hybridization, we identify G-protein coupled receptor, Gpr37, as a gene expressed only in EGCs of the myenteric plexus, one of the two layers of the ENS. We show that Gpr37 contributes to key components of LPS-induced reactive gliosis including activation of NF-kB and IFN-y signaling and response genes, lymphocyte recruitment, and inflammation-induced GI dysmotility. Targeting Gpr37 in EGCs presents a potential avenue for modifying inflammatory processes in the ENS.
2025-06-24 | GSE262418 | GEO
Project description:Influence of 3,5,3'-Triiodothyronine (T3) on differentiating progenitor cells of the enteric nervous system (ENS)
| PRJNA171308 | ENA
Project description:The proper organization of the enteric nervous system (ENS) is critical for normal gastrointestinal (GI) physiology. Inflammatory bowel disease (IBD) dysregulates GI physiology including bowel movements (motility), but in many IBD patients, GI motility disorders persist in remission through a poorly understood pathological process. Here we uncover that post-inflammatory GI dysmotility (PI-GID) stems from structural ENS remodeling driven by a combination of neuronal loss and neurogenesis. Enteric neurons respond to mucosal inflammation by upregulating CCL2 expression and facilitating the recruitment of CCR2+ monocytes into the neural myenteric plexus of the intestinal muscle followed by the expansion of monocyte-derived macrophages, their migration into the myenteric ganglia and phagocytosis of neurons. However, excessive recruitment of monocytes promotes disproportionate ENS remodeling and PI-GID. Expansion of immune cells in the tissue also promotes tissue hypoxia. We find that enteric neurons are hypoxic upon colitis; hypoxia-induced signaling via HIF1alpha induces an adaptation program in enteric neurons to suppress CCL2 expression and limit monocyte recruitment. We demonstrate that reinforcing HIF1alpha signaling in enteric neurons prevents PI-GID by reducing colitis-associated monocyte recruitment in the myenteric plexus and mitigating ENS remodeling. In summary, our findings unveil PI-GID pathogenesis and identify a regulatory axis for its prevention.
2026-01-08 | GSE266254 | GEO
Project description:The proper organization of the enteric nervous system (ENS) is critical for normal gastrointestinal (GI) physiology. Inflammatory bowel disease (IBD) dysregulates GI physiology including bowel movements (motility), but in many IBD patients, GI motility disorders persist in remission through a poorly understood pathological process. Here we uncover that post-inflammatory GI dysmotility (PI-GID) stems from structural ENS remodeling driven by a combination of neuronal loss and neurogenesis. Enteric neurons respond to mucosal inflammation by upregulating CCL2 expression and facilitating the recruitment of CCR2+ monocytes into the neural myenteric plexus of the intestinal muscle followed by the expansion of monocyte-derived macrophages, their migration into the myenteric ganglia and phagocytosis of neurons. However, excessive recruitment of monocytes promotes disproportionate ENS remodeling and PI-GID. Expansion of immune cells in the tissue also promotes tissue hypoxia. We find that enteric neurons are hypoxic upon colitis; hypoxia-induced signaling via HIF1alpha induces an adaptation program in enteric neurons to suppress CCL2 expression and limit monocyte recruitment. We demonstrate that reinforcing HIF1alpha signaling in enteric neurons prevents PI-GID by reducing colitis-associated monocyte recruitment in the myenteric plexus and mitigating ENS remodeling. In summary, our findings unveil PI-GID pathogenesis and identify a regulatory axis for its prevention.
2026-01-08 | GSE263945 | GEO
Project description:The enteric nervous system (ENS) can control most essential gut functions owing to its organization into complete neural circuits consisting of a multitude of different neuronal subtypes. We used microarrays to identify transcription factor networks and signaling pathways involved in diversification and differentiation of enteric neurons during development of the enteric nervous system.
2017-12-05 | GSE100130 | GEO