Regulation of intestinal epithelial cells transcriptome by enteric glial cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE17027 | GEO | 2009/07/10
SECONDARY ACCESSION(S): PRJNA117791
REPOSITORIES: GEO
Similar Datasets
Project description:Identification of cellular functions and signalling pathways of intestinal epithelial cells modulated by enteric glial cells Keywords: Transcriptome regulation Two-condition experiment (intestinal epithelial cells cultured in absence or in presence of enteric glial cells) with 3 time points (t=0, 8 and 24h). 4 Biological replicates/condition. Every replicate was hybridized against a reference pool composed by a mix of the 4 replicates of t=0 condition in equal quantity.
2010-05-16 | E-GEOD-17027 | biostudies-arrayexpress
Project description:Enteric glia are the predominant cell type in the enteric nervous system yet their identities and roles in gastrointestinal function are not well classified. Using our optimized single nucleus RNA-sequencing method, we identified distinct molecular classes of enteric glia and defined their morphological and spatial diversity. Our findings revealed a functionally specialized biosensor subtype of enteric glia that we call “hub cells.” Deletion of the mechanosensory ion channel PIEZO2 from adult enteric glial hub cells, but not other subtypes of enteric glia, led to defects in intestinal motility and gastric emptying in mice. These results provide insight into the multifaceted functions of different enteric glial cell subtypes in gut health and emphasize that therapies targeting enteric glia could advance the treatment of gastrointestinal diseases.
2023-09-08 | GSE232703 | GEO
Project description:Enteric glial hub cells coordinate intestinal motility
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Project description:Intestinal ganglionic cells in the adult enteric nervous system (ENS) are continually exposed to stimuli from the surrounding microenvironment, and need at times to respond to disturbed homeostasis following acute intestinal injury. The kinase DCLK1 and intestinal Dclk1-positive cells have been reported to contribute to intestinal regeneration. While Dclk1-positive cells are present in adult enteric ganglia, their cellular identity and response to acute injury have not been investigated in detail. Here, we reveal the presence of distinct Dclk1-tdTom+/CD49b+ glial-like and Dclk1-tdTom+/CD49b- neuronal cell types in adult myenteric ganglia. These ganglionic cells demonstrate distinct patterns of tracing over time, yet show a similar expansion in response to elevated serotonergic signaling. Interestingly, Dclk1-tdTom+ glial-like and neuronal cell types appear resistant to acute irradiation injury-mediated cell death. Moreover, Dclk1-tdTom+/CD49b+ glial-like cells show prominent changes in gene expression profiles induced by injury, in contrast to Dclk1-tdTom+/CD49b- neuronal cell types. Finally, subsets of Dclk1-tdTom+/CD49b+ glial-like cells demonstrate prominent overlap with Nestin and p75NTR, and strong responses to elevated serotonergic signaling or acute injury. These findings, together with their role in early development and their neural-crest like gene expression signature, suggest the presence of reserve progenitor cells in the adult Dclk1 glial cell lineage.
2021-10-31 | GSE156031 | GEO
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
Project description:Glial Guidance Drives Postnatal Intestinal Reinnervation by Enteric Neurons
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Project description:Enteric glial cells are important players in the control of motility, intestinal barrier integrity and inflammation. During inflammation, they switch into a reactive phenotype enabling them to release inflammatory mediators, thereby shaping the inflammatory environment. While a plethora of well-established in vivo models exist, cell culture models necessary to decipher the mechanistic pathways of enteric glial reactivity are less well standardized. In particular, the composition of extracellular matrices (ECM) can massively affect the experimental outcome. Considering the growing number of studies involving primary enteric glial cells, a better understanding of their homeostatic and inflammatory in vitro culture conditions is needed. We examined the impact of different ECMs on enteric glial culture homeostasis and immune responsiveness. We used 3’ bulk mRNA sequencing to compare cultured cells with in vivo enteric glial transcriptomes isolated from Sox10iCreERT2Rpl22HA/+ mice. Transcriptional analysis revealed strong similarities between enteric glia on Matrigel and laminin with enrichment of gene sets supporting neuronal differentiation, while cells on poly-L-ornithine showed enrichment related to cell proliferation. Comparing cultured and in vivo enteric glial transcriptomes revealed a 50% overlap. IL-1β treatment showed distinct coating-dependent gene expression signatures, with an enrichment of genes related to myeloid and epithelial cell differentiation on Matrigel and laminin coatings, while poly-L-ornithine induced more gene sets related to lymphocyte differentiation. Together, changes in differentiation and immune activation of primary enteric glial cells proved a strong effect of the ECM. We identified Matrigel and laminin as pre-eminent substrates for murine enteric glial cultures. These new insights will help to standardize and improve enteric glial culture quality and reproducibility between studies in the future, allowing a better comparison of their functional role in enteric neuroinflammation.
2024-08-15 | GSE271114 | GEO
Project description:Proteomic study on the protective effect of black wolfberry polysaccharide extract on high blood glucose induced damage to enteric glial cells
2024-07-27 | PXD054469 |
Project description:Glial cells have been proposed as an endogenous source of progenitors for the treatment of neural deficits. However, the cellular and molecular mechanisms underpinning the neurogenic potential of certain populations of adult glial cells, are not known. Using single cell transcriptomic profiling, we show here that enteric glial cells represent a cell state attained by autonomic neural crest cells as they transition during development along a linear default differentiation trajectory that allows them to retain neurogenic potential while acquiring a gene expression profile associated with their role in neuronal support and immunomodulation. Key neurogenic loci in early enteric nervous system progenitors remain in open chromatin configuration in mature enteric glia, thus facilitating neuronal differentiation under appropriate conditions. Molecular profiling and gene targeting of enteric glial cells in a novel cell culture system of enteric neurogenesis and a gut injury model, demonstrated that neuronal differentiation of glia is driven by transcriptional programs employed in vivo by early progenitors. Our work provides mechanistic insight into the dynamic regulatory landscape underpinning the development of intestinal neural circuits and generates a platform for advancing glial cells as therapeutic agents for the treatment of neural deficits.
2023-07-31 | GSE239305 | GEO
Project description:BACKGROUND Enteric glia contribute to the pathophysiology of various intestinal immune-driven diseases, such as postoperative ileus (POI), a motility disorder and common complication after abdominal surgery. Enteric gliosis of the intestinal muscularis externa (ME) has been identified as part of POI development. However, the glia-restricted responses and activation mechanisms are poorly understood. The sympathetic nervous system becomes rapidly activated by abdominal surgery. It modulates intestinal immunity, innervates all intestinal layers, and directly interfaces with enteric glia. We hypothesized that sympathetic innervation controls enteric glia reactivity in response to surgical trauma. METHODS Sox10iCreERT2/Rpl22HA/+ mice were subjected to a mouse model of laparotomy or intestinal manipulation to induce POI. Histological, protein, and transcriptomic analyses were performed to analyze glia-specific responses. Interactions between the sympathetic nervous system and enteric glia were studied in mice chemically depleted of TH+ sympathetic neurons and glial-restricted Sox10iCreERT2/JellyOPfl/+/Rpl22HA/+ mice, allowing optogenetic stimulation of β-adrenergic downstream signaling and glial-specific transcriptome analyses. A laparotomy model was used to study the effect of sympathetic signaling on enteric glia in the absence of intestinal manipulation. Mechanistic studies included adrenergic receptor expression profiling in vivo and in vitro and adrenergic agonism treatments of primary enteric glial cell cultures to elucidate the role of sympathetic signaling in acute enteric gliosis and POI. RESULTS With ~4000 differentially expressed genes, the most substantial enteric glia response occurs early after intestinal manipulation. During POI, enteric glia switch into a reactive state and continuously shape their microenvironment by releasing inflammatory and migratory factors. Sympathetic denervation reduced the inflammatory response of enteric glia in the early postoperative phase. Optogenetic and pharmacological stimulation of β-adrenergic downstream signaling triggered enteric glia reactivity. Finally, distinct adrenergic agonists revealed β-1/2 adrenoceptors as the molecular targets of sympathetic–driven enteric glial reactivity. CONCLUSIONS Enteric glia act as early responders during post-traumatic intestinal injury and inflammation. Intact sympathetic innervation and active β-adrenergic receptor signaling in enteric glia is a trigger of the immediate glial postoperative inflammatory response. With immune-activating cues originating from the sympathetic nervous system as early as the initial surgical incision, adrenergic signaling in enteric glia presents a promising target for preventing POI development.
2023-11-15 | GSE198889 | GEO