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Comparative transcriptomics reveal highly conserved regional programs between porcine and human colonic enteric nervous system

ABSTRACT: Comparative transcriptomics reveal highly conserved regional programs between porcine and human colonic enteric nervous system

PROVIDER: PRJNA809006 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR18090503.fastq.gz	Fastqsanger.gz
	SRR18090504.fastq.gz	Fastqsanger.gz
	SRR18090505.fastq.gz	Fastqsanger.gz
	SRR18090506.fastq.gz	Fastqsanger.gz
	SRR18090507.fastq.gz	Fastqsanger.gz

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Comparative transcriptomics reveal highly conserved regional programs between porcine and human colonic enteric nervous system

Project description:The enteric nerve system (ENS) coordinates diverse gastrointestinal functions. The porcine gastrointestinal tract is increasingly regarded as a useful translational model. However, porcine ENS molecular profiling and its similarity to that of human are lacking. Bulk RNA sequencing (RNA-seq) coupled with laser-capture microdissection and single-cell RNA-seq on myenteric ganglia (MG) addressed that discrepant transcriptional programs explained the functional characteristics between inner submucosal and/or MG in porcine proximal or/and distal colon (p-pC, p-dC). Comparative bulk transcriptomics of MG in corresponding colonic regions of porcine and human revealed highly conserved programs existing in p-pC and p-dC, which interpreted >90% of their transcriptomic responses to vagal nerve stimulation (VNS), suggesting that p-pC and p-dC could serve as predictors in translational studies. At bulk and single-cell resolution, we highlighted specific conserved programs, executing inflammatory modulation in porcine with VNS. This study offers rich foundations to understand human colonic functions and neuromodulation using porcine model.

2023-01-22 | GSE197106 | GEO

Comparative transcriptomics reveals highly conserved regional programs between porcine and human colonic enteric nervous system.

Project description:The porcine gut is increasingly regarded as a useful translational model. The enteric nervous system in the colon coordinates diverse functions. However, knowledge of the molecular profiling of porcine enteric nerve system and its similarity to that of human is still lacking. We identified the distinct transcriptional programs associated with functional characteristics between inner submucosal and myenteric ganglia in porcine proximal and distal colon using bulk RNA and single-cell RNA sequencing. Comparative transcriptomics of myenteric ganglia in corresponding colonic regions of pig and human revealed highly conserved programs in porcine proximal and distal colon, which explained >96% of their transcriptomic responses to vagal nerve stimulation, suggesting that porcine proximal and distal colon could serve as predictors in translational studies. The conserved programs specific for inflammatory modulation were displayed in pigs with vagal nerve stimulation. This study provides a valuable transcriptomic resource for understanding of human colonic functions and neuromodulation using porcine model.

| S-EPMC9872754 | biostudies-literature

RNA Expression Data from developing enteric nervous system (ENS) and bowel

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

Impact of 6-mercaptopurine on LPS treated primary cultures of enteric nervous system

Project description:Enteric nervous system is involved in the regulation of intestinal inflammation. We developped mouse primary cultures of enteric nervous system to study impact of LPS, as pro-inflammatory mediator, and of the pro-drug 6-mercaptopurine on enteric inflammatory pathways We used microarrays to detail the global programme of gene expression underlying enteric neuro-inflammation and identified classes of up-regulated genes during this process.

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Toxic Exposure of Pyridostigmine Bromide Chronically Impairs Colonic Motility Via Low Grade Enteric Neuroinflammation

Project description:Combat veterans from the Persian Gulf War have unexplained yet persistent impairment in colonic motility due to combat-related toxic exposures. Central to Gulf War-related toxic exposures was the unmitigated ingestion of Pyridostigmine bromide (PB). We previously developed a Gulf War Illness (GWI) mouse model, where acute PB exposure led to immediate disruptions in colonic motility. Here, we explore mechanisms by which acute enteric neuroinflammation produces peristent impairment in colonic motility. GWI mice were exposed to PB transiently, and allowed to recover with no exposures for 1 month. GWI mice had significantly increased amplitudes of colonic contraction and diminished nerve-stimulated colonic relaxation, compared to naive controls. Immunohistological characterization demonstrated persistent chronic damage in enteric neuronal network integrity, accompanied by a significant imbalance in excitatory and inhibitory motor neuronal populations. Inflammatory CD40+ tissue- resident macrophages were identified with enteric neural stem cells in GWI colons, with an increase in secreted inflammatory cytokines. Unbiased transcriptomic analysis corroborated peristent low grade enteric neuroinflammation, overall resulting in impaired repair and regeneration of neural circuity in GWI. Our learnings can be leveraged to design new regenerative therapies for Gulf War veterans, and broadly impact our understanding of severeal inflammatory disorders of the gut.

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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.

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Lineage-dependent spatial and functional organisation of the mammalian enteric nervous system

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Expression analysis of adult zebrafish enteric nervous system

Project description:The enteric nervous system (ENS) encompasses the intrinsic neuroglia networks of the gastrointestinal (GI) tract that are essential for digestive function and gut homeostasis. To investigate the ENS of zebrafish, we carried out bulk RNA sequencing on nuclei purified by FACS (fluorescent-activated cell sorting) representing both the Cherry+ (ENS) and Cherry- (non-ENS) muscularis externa cell populations of Tg(sox10:Cre;Cherry) zebrafish gut.

2020-09-14 | GSE145885 | GEO

Expression analysis of adult zebrafish enteric nervous system

Project description:Expression analysis of adult zebrafish enteric nervous system

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Cell-autonomous retinoic acid receptor signaling alters enteric nervous system development with stage-specific effects in mice

Project description:Purpose: Determine how blocking retinoic acid receptor (RAR) signaling within enteric neural crest-derived cells (ENCDC) from E11.5 stomach or E13.5 colon alters mRNA abundance. These ENCDC become the enteric nervous system. Methods: Enteric nervous system precursors were isolated from mouse E11.5 stomach or E13.5 colon using fluorescence activated cell sorting to purify TdTomato or EYFP expressing cells respectively from fetal bowel. The RarαDN allele encodes a potent RAR dominant negative protein that is expressed after CRE-mediated DNA recombination. Tamoxifen-activated CRE-ERT2 was expressed from the Ret locus for E13.5 colon studies and mice were tamoxifen treated at E10.5 prior to cell sorting. The Wnt1Cre allele was employed for E11.5 stomach studies. RNA-SEQ was performed in quadruplicate using Illumina HiSeq 4000. Sequence reads that passed quality filters were aligned to remove repeat sequences and ribosomal RNA reads and then processed using RNA-Seq unified mapper (RUM) package. RUM files were visualized in the TessLA browser for subsequent analyses. Results: Transcriptional profiling shows RarαDN differentially impacts gene expression in E11.5 stomach and E13.5 colon enteric neural crest-derived cells (ENCDC) that become the enteric nervous system. Conclusions: Blocking of RAR signaling in ENCDC causes dramatic changes in gene expression during early development in a stage-specific manner.

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