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Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with gastroparesis

ABSTRACT: Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with gastroparesis

PROVIDER: PRJNA531171 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR8859680_1.fastq.gz	Fastqsanger.gz
	SRR8859680_2.fastq.gz	Fastqsanger.gz
	SRR8859690_1.fastq.gz	Fastqsanger.gz
	SRR8859690_2.fastq.gz	Fastqsanger.gz
	SRR8859700_1.fastq.gz	Fastqsanger.gz

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Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with gastroparesis

Project description:The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in gastroparesis and obesity.

2019-06-21 | GSE129398 | GEO

Transcriptome profiling reveals significant changes in the gastric muscularis externa with obesity that partially overlap those that occur with idiopathic gastroparesis.

Project description:BackgroundGastric emptying is impaired in patients with gastroparesis whereas it is either unchanged or accelerated in obese individuals. The goal of the current study was to identify changes in gene expression in the stomach muscularis that may be contributing to altered gastric motility in idiopathic gastroparesis and obesity.MethodsQuantitative real time RT-PCR and whole transcriptome sequencing were used to compare the transcriptomes of lean individuals, obese individuals and either lean or obese individuals with idiopathic gastroparesis.ResultsObesity leads to an increase in mRNAs associated with muscle contractility whereas idiopathic gastroparesis leads to a decrease in mRNAs associated with PDGF BB signaling. Both obesity and idiopathic gastroparesis were also associated with similar alterations in pathways associated with inflammation.ConclusionsOur findings show that obesity and idiopathic gastroparesis result in overlapping but distinct changes in the gastric muscularis transcriptome. Increased expression of mRNAs encoding smooth muscle contractile proteins may be contributing to the increased gastric motility observed in obese subjects, whereas decreased PDGF BB signaling may be contributing to the impaired motility seen in subjects with idiopathic gastroparesis.

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Bulk RNA-sequencing of self-maintaining versus monocyte-replaced gut macrophages

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Neuro-immune Crosstalk in the Enteric Nervous System from Early Postnatal Development to Adulthood

Project description:Single-cell RNA sequencing using SmartSEQ2 platform of Cx3cr1+ macrophages isolated from the muscularis externa of mice of 10 and of 56 days of age.

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Resolving Resident Colonic Muscularis Macrophage Diversity and Plasticity During Colitis

Project description:Background: Immune cell populations within the intestinal muscularis propria are poorly resolved during colitis. Maintaining homeostasis in this unique niche is of critical importance, highlighted by the poorer prognosis of inflammatory bowel disease associated with inflammation in the muscularis propria. Methods: This study utilizes single-cell RNA sequencing to survey the immune cell populations within the muscularis propria of normal colon and DSS-induced colitis. Results: In naïve conditions, transcriptional duality is observed in MMφ with two major supopulations: conventional resident Cx3cr1+ MMφs and Lyve1+ MMφs. During colitis, significant changes occur within the muscularis propria, with increases in B-cells, T-cells, monocytes, neutrophils, and dendritic cells. Unlike in the mucosa, single cell transcriptomics indicates that resident MMφs are retained during colitis and exhibit plasticity toward an inflammatory profile. Lyve1+ MMφs, which express anti-inflammatory marker CD163, are absent during colitis. In contrast, resident Cx3cr1+ MMφs remain during colitis. Conclusions: Our findings provide a resource for understanding the immune system in the muscularis propria niche during colitis and resolve the heterogeneity and origins of proinflammatory MMφs during colitis by demonstrating the plasticity of the persistent MMφ population.

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Comparison between lamina propria macrophages and muscularis macrophages

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Enteric glial cells favor accumulation of anti-inflammatory macrophages during the resolution of muscularis inflammation

Project description:Monocyte-derived macrophages (Mφs) are crucial regulators during muscularis inflammation. However, it is unclear which micro-environmental factors are responsible for monocyte recruitment and anti-inflammatory Mφ differentiation in this paradigm. Here, we investigate Mφ heterogeneity at different stages of muscularis inflammation and determine how environmental cues can attract and activate tissue-protective Mφs. Results showed that muscularis inflammation induced marked alterations in mononuclear phagocyte populations associated with a rapid infiltration of Ly6c+ monocytes that locally acquired unique transcriptional states. Trajectory inference analysis revealed two main pro-resolving Mφ subpopulations during the resolution of muscularis inflammation, i.e. Cd206+ MhcIIhi and Timp2+ MhcIIlo Mφs. Interestingly, we found that damage to the micro-environment upon muscularis inflammation resulted in EGC activation, which in turn stimulated monocyte infiltration and the consequent differentiation in anti-inflammatory CD206+ Mφs via CCL2 and CSF1, respectively. In addition, CSF1-CSF1R signaling was shown to be essential for the differentiation of monocytes into CD206+ Mφs and EGC proliferation during muscularis inflammation. Our study provides a comprehensive insight into pro-resolving Mφ differentiation and their regulators during muscularis inflammation. We deepened our understanding in the interaction between EGCs and Mφs, thereby highlighting pro-resolving Mφ differentiation as a potential novel therapeutic strategy for the treatment of intestinal inflammation.

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Enteric glial cells favor accumulation of anti-inflammatory macrophages during the resolution of muscularis inflammation

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