Enteric nervous system: timecourse analysis of longitudinal muscle and myenteric plexus (LMMP) in mice
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE213604 | GEO | 2023/02/06
REPOSITORIES: GEO
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Project description:This study was undertaken to define the molecular subtypes of myenteric plexus glial cells in mice, and to understand the molecular basis for glial cells’ capacity to become neurons. Methods: We performed single-cell RNA sequencing and single-nucleus ATAC sequencing of enteric neurons from small intestine at the adolescent mice (on or near postnatal day of life 14). We also performed both single-cell RNA sequencing and single-nucleus ATAC sequencing on 3-dimensional neurosphere cultures. Results: We identify numerous distinct transcriptional subgroups of myenteric plexus glial cells, including cells expressing genes associated with neuronal differentiation. Epigenetic analysis shows distinct chromatin accessibility profiles that correlate with gene expression patterns. Glial cells maintain open chromatin at gene loci associated with neuronal fate. 3-dimensional cultures provide a niche for active neurogenesis. Chromatin closes at glial-associate loci during neurogenesis. Conclusion: Utilizing single-cell RNA sequencing and single-nucleus ATAC sequencing, we identify myenteric glial cell subtypes and uncover a molecular basis for a glial-to-neuronal fate transition.
2023-03-02 | GSE184981 | GEO
Project description:Interstitial cells of Cajal (ICC) have important functions in regulation of motor activity in the gastrointestinal tract. In murine small intestine ICC are gathered in the region of the myenteric plexus (ICC-MY) and within the deep-muscular plexus near the submucosal surface of the circular muscle layer (ICC-DMP). These two classes of ICC have different physiological functions. ICC-MY are pacemaker cells and generate the slow wave electrical rhythmicity of gastrointestinal organs. ICC-DMP form synaptic connections with the varicose nerve terminals of enteric motor neurons and are involved in reception and transduction of motor neurotransmission. In the present study we used recently developed highly selective techniques to isolate the two classes of ICC from enzymatically dispersed intestinal muscles by fluorescence-activated cell sorting. Transcriptional expression of the two functional classes was investigated using DNA microarray analysis. Experiment Overall Design: ICC-DMP and ICC-MY cells were isolated from the murine small intestinal tissues and their transcriptional expression was compared with that of the tunica muscularis tissues. Transcriptional expression profiles of ICC-DMP and ICC-MY were compared to each other also.
2008-06-15 | E-GEOD-7809 | biostudies-arrayexpress
Project description:The data provided here were used to generate a comprehensive transcriptome atlas for the human myenteric plexus from healthy human adults
2020-10-12 | GSE153198 | GEO
Project description: Not available
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Project description:MMP (muscularis myenteric plexus) RNAseq profilings in Germ-free (GF) colons with microbe stimulations
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Project description:Bowel function requires coordinated activity of many enteric neuron subtypes. Clear definition of subtype-specific gene expression may facilitate molecular diagnoses for bowel motility disorders. Using adult mouse colon RNAseq data from 635 myenteric neurons and 707 E17.5 neurons, we defined seven adult myenteric neuron subtypes, eight E17.5 neuron subtypes and hundreds of differentially-expressed genes. Manually dissected human colon myenteric plexus yielded data from 48 neurons, 3798 glia, 5568 smooth muscle, 377 interstitial cells, and 2153 macrophages. Immunohistochemistry demonstrated differential protein abundance for BNC2, PBX3, RBFOX1, TBX2, and TBX3 in enteric neuron subtypes. Conditional Tbx3 loss reduced NOS1-expressing myenteric neurons. Differential Gfra1 and Gfra2 expression coupled with calcium imaging revealed that GDNF and neurturin acutely and differentially regulate activity of ~50% of myenteric neurons with distinct effects on smooth muscle contractions. This insight into enteric nervous system biology provides a foundation for future studies of bowel motility disorders.
2021-01-01 | GSE156905 | GEO
Project description:For most multigenic disorders, clinical manifestation (penetrance) and presentation (expressivity) are likely to be an outcome of genetic interaction between multiple susceptibility genes. Here, using gene knockouts in mice we evaluated genetic interaction between loss of Ret and loss of Sema3d, two Hirschsprung disease (HSCR) susceptibility genes. We intercrossed Ret and Sema3d double null heterozygotes to generate mice with the nine possible genotypes and assessed survival by counting various genotypes, myenteric plexus development by acetylcholinesterase (AchE) staining and embryonic day 12.5 (E12.5) gut transcriptome by RNA-sequencing. Survival rates of Ret wildtype, null heterozygote and null homozygote mice at E12.5, birth and weaning were not influenced by the genotypes at Sema3d locus and vice-versa. Loss of myenteric plexus was observed only in all Ret null homozygotes, irrespective of the genotypes at Sema3d locus, and Sema3d null heterozygote and homozygote mice had normal gut innervation. As compared to wildtype mice gut gene expression, loss of Ret in null homozygotes led to differential expression of ~300 genes, whereas loss of Sema3d in null homozygotes had no major consequence and there was no evidence supporting major interaction between the two genes influencing gut transcriptome. Overall, given the null alleles and phenotypic assays used, we did not find evidence for genetic interaction between Ret and Sema3d affecting survival, myenteric plexus formation or gut transcriptome.
2017-03-28 | GSE89627 | GEO
Project description:Objective: To assess the development of neuronal subtypes and the emergence of evoked electrical activity within the developing human ENS. Methods: Human foetal gut samples were obtaining via the MRC-Wellcome Trust Human Developmental Biology Resource (UK). Characterisation of the developing ENS was performed by immunohistochemistry, calcium imaging, RNAseq and qRT-PCR Results: Human foetal colon samples displayed robust Tuj1 immunohistochemistry by embryonic week (EW) 12 with a dense neuronal network at the level of the myenteric plexus. At EW12 expression of excitatory neurotransmitter markers (VAChT and Sub P) was observed. By contrast, inhibitory neurotransmitter markers (nNOS and VIP) were not observed until EW14. Co-labeling with synaptic markers (SYN1/SNAP-25) demonstrated the development of synaptic contacts by EW12. However, electrical train stimulation (40V,2s,20Hz of 300?s electrical pulses) did not evoke activity within the myenteric plexus of EW12 foetal gut (n=0/3). Similarly, the majority of EW14 gut tissues assessed (80%), demonstrated no response to electrical stimulation (n=4/5). Interestingly, at EW16 Tuj1+ expression, in the myenteric plexus, was observed within discrete ganglia and was combined with the emergence of calcium transients (F/F0=1.273±0.024;n=3), upon electrical stimulation (n=3/3), which were abolished after the addition of 1uM TTX (n=3/3). RNAseq and qRT-PCR analysis between EW12-16 revealed increases in expression in genes involved in neurotransmission and action potential generation including SCN9A and KCNQ3. Conclusion: Here we demonstrate the temporal development of human enteric neuronal subtypes from EW12-14 and the subsequent emergence of coordinated electrical activity within the human foetal ENS at approximately EW16.
2019-02-20 | GSE111307 | GEO
Project description:Postoperative ileus (POI) is triggered by an innate immune response in the muscularis externa (ME) and is accompanied by bacterial translocation. Bacteria can trigger an innate immune response via toll-like receptor (TLR) activation, but the latter’s contribution to POI has been disproved for several TLRs, including TLR2 and TLR4. Herein we investigated the role of double-stranded RNA detection via TLR3 and TIR-domain-containing adapter inducing interferon-b (TRIF) signaling pathway in POI. POI was induced by small bowel intestinal manipulation in wt, TRIF-/-, TLR3-/-, type I interferon receptor-/- and interferon-b reporter mice, all on C57BL/6 background, and POI severity was quantified by gene expression analysis, gastrointestinal transit, and leukocyte extravasation into the ME. TRIF/ TLR3 deficiency reduced postoperative ME inflammation and prevented POI. With bone marrow transplantation, RNA-sequencing, flow cytometry, and immunohistochemistry we revealed a distinct TLR3-expressing radio-resistant MHCIIhiCX3CR1- IBA-1+ resident macrophage population within the deep myenteric plexus. TLR3 deficiency in these cells, but not in MHCIIhiCX3CR1+ macrophages, reduced cytokine expression in POI. While this might not be an exclusive macrophage-privileged pathway, the TLR3/TRIF axis contributes to proinflammatory cytokine production in MHCIIhiCX3CR1- IBA-1+ macrophages during POI. Deficiency in TLR3/TRIF protects mice from POI. These data suggest that TLR3 antagonism may prevent POI in humans.
2022-02-21 | GSE132147 | GEO
Project description:Atoh1-Cre; Myc/Myc mice developed choroid plexus papilloma and Atoh1-Cre; Myc/Myc; p53fl/fl mice developed choroid plexus carcinoma. By studying the gene expression profiles of normal choroid plexus, choroid plexus papilloma and choroid plexus carcinoma in mice, we aim to gain a better understanding of the biology of choroid plexus tumors
2019-05-01 | GSE126327 | GEO