The smooth muscle-specific lncRNA Carmn is required for visceral smooth muscle contractile function
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE199157 | GEO | 2023/09/23
REPOSITORIES: GEO
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Project description:DNA methylation is a key epigenetic modification that can regulate gene expression. Genomic DNA hypomethylation is commonly found in many gastrointestinal (GI) diseases. Dysregulated gene expression in GI smooth muscle cells (GI-SMC) can lead to motility disorders. However, the consequences of genomic DNA hypomethylation within GI-SMC are still elusive. Utilizing a Cre-lox murine model, we have generated SMC-restricted DNA methyltransferase 1 (Dnmt1) knockout (KO) mice and analyzed the effects of Dnmt1 deficiency. Dnmt1-KO pups are born smaller than their wild type littermates, have shortened GI tracts, lose peristaltic movement due to loss of the tunica muscularis in their intestine, causing massive intestinal dilation, and death around post-natal day 21. Within smooth muscle tissue, significant CpG hypomethylation occurs across the genome at promoters, introns and exons. Additionally, there is a marked loss of differentiated SMC markers (Srf, Myh11, miR-133, miR-143/145), an increase in pro-apoptotic markers (Nr4a1, Gadd45g), loss of cellular connectivity, and an accumulation of coated vesicles within SMC. Interestingly, we observed consistent abnormal expression patterns of enzymes involved in DNA methylation between both ¬Dnmt1-KO mice and diseased human GI tissue. These data demonstrate that DNA hypomethylation in embryonic SMC, via congenital Dnmt1 deficiency, contributes to massive dysregulation of gene expression and is lethal to GI-SMC. These results suggest that Dnmt1 has a necessary role in the embryonic, primary development process of SMC with consistent patterns being found in human GI diseased tissue.
2018-02-13 | GSE109273 | GEO
Project description:DNA methylation is a key epigenetic modification that can regulate gene expression. Genomic DNA hypomethylation is commonly found in many gastrointestinal (GI) diseases. Dysregulated gene expression in GI smooth muscle cells (GI-SMC) can lead to motility disorders. However, the consequences of genomic DNA hypomethylation within GI-SMC are still elusive. Utilizing a Cre-lox murine model, we have generated SMC-restricted DNA methyltransferase 1 (Dnmt1) knockout (KO) mice and analyzed the effects of Dnmt1 deficiency. Dnmt1-KO pups are born smaller than their wild type littermates, have shortened GI tracts, lose peristaltic movement due to loss of the tunica muscularis in their intestine, causing massive intestinal dilation, and death around post-natal day 21. Within smooth muscle tissue, significant CpG hypomethylation occurs across the genome at promoters, introns and exons. Additionally, there is a marked loss of differentiated SMC markers (Srf, Myh11, miR-133, miR-143/145), an increase in pro-apoptotic markers (Nr4a1, Gadd45g), loss of cellular connectivity, and an accumulation of coated vesicles within SMC. Interestingly, we observed consistent abnormal expression patterns of enzymes involved in DNA methylation between both ¬Dnmt1-KO mice and diseased human GI tissue. These data demonstrate that DNA hypomethylation in embryonic SMC, via congenital Dnmt1 deficiency, contributes to massive dysregulation of gene expression and is lethal to GI-SMC. These results suggest that Dnmt1 has a necessary role in the embryonic, primary development process of SMC with consistent patterns being found in human GI diseased tissue.
2018-02-13 | GSE109272 | GEO
Project description:DNA methylation is a key epigenetic modification that can regulate gene expression. Genomic DNA hypomethylation is commonly found in many gastrointestinal (GI) diseases. Dysregulated gene expression in GI smooth muscle cells (GI-SMC) can lead to motility disorders. However, the consequences of genomic DNA hypomethylation within GI-SMC are still elusive. Utilizing a Cre-lox murine model, we have generated SMC-restricted DNA methyltransferase 1 (Dnmt1) knockout (KO) mice and analyzed the effects of Dnmt1 deficiency. Dnmt1-KO pups are born smaller than their wild type littermates, have shortened GI tracts, lose peristaltic movement due to loss of the tunica muscularis in their intestine, causing massive intestinal dilation, and death around post-natal day 21. Within smooth muscle tissue, significant CpG hypomethylation occurs across the genome at promoters, introns and exons. Additionally, there is a marked loss of differentiated SMC markers (Srf, Myh11, miR-133, miR-143/145), an increase in pro-apoptotic markers (Nr4a1, Gadd45g), loss of cellular connectivity, and an accumulation of coated vesicles within SMC. Interestingly, we observed consistent abnormal expression patterns of enzymes involved in DNA methylation between both ¬Dnmt1-KO mice and diseased human GI tissue. These data demonstrate that DNA hypomethylation in embryonic SMC, via congenital Dnmt1 deficiency, contributes to massive dysregulation of gene expression and is lethal to GI-SMC. These results suggest that Dnmt1 has a necessary role in the embryonic, primary development process of SMC with consistent patterns being found in human GI diseased tissue.
2018-02-13 | GSE109641 | GEO
Project description:Genome scale expression data on absolute numbers of gene isoforms offer essential clues for cellular functions and biological processes. Gastrointestinal (GI) motility is regulated by smooth muscle cells (SMC) closely contacted with interstitial cells of Cajal (ICC) and fibroblast-like PDGFRα+ cells (PαC), forming an electrical syncytium. To uncover genetic identifies and cellular functions of the cells, we isolated these three cell populations from mouse small intestine and colon, obtained the transcriptome for each type of cells, and built each cell type transcriptome browser. To our knowledge, this is the first genetic resource providing a comprehensive reference for all mRNA transcripts expressed in these unique GI cell populations. Integration of these data with the UCSC genome browser revealed novel cell-specific markers, ion channel and transporter isoforms, and unique cellular and biological functions of these cells in GI physiology. Our transcriptome browsers bring new insight into the alternative expression of genes in different types of the cells and provides references for future functional studies. mRNA profiles of SMC, ICC and PDGFRa cells isolated from mouse jejunum and colon were generated by deep sequencing using Illumina Hiseq2000..
2015-07-31 | E-GEOD-57776 | biostudies-arrayexpress
Project description:The etiology of post-inflammatory gastrointestinal (GI) motility dysfunction, after resolution of acute symptoms of inflammatory bowel diseases (IBD) and intestinal infection, is largely unknown. Here, using an established mouse model of experimental enteritis, we show that enhancement of smooth muscle cell (SMC) contraction by interleukin (IL)-17A may be involved in postinflammatory GI hypermotility. To examine the effect of IL-17 in the small intestinal smooth muscle, we used whole genome microarray expression profiling to find out the genes which respond to IL-17 stimulus. The smooth muscle strips were peeled off from mouse small intestine and incubated 24h with or without IL-17. And we also examined the effect of 6-shogaol, which is one of the ingredients of Japanese traditional medicine for intestinal mortor disorder, Daikenchuto, in IL-17 stimulated small intestinal smooth muscle strip. The smooth muscle strips were peeled off from mice small intestine and incubated in the culture media for 24h with or without IL-17. A part of IL-17 stimulated strips were co-incubated with 6-shogaol. Six independent experiments were performed.
2012-09-15 | E-GEOD-39573 | biostudies-arrayexpress
Project description:The etiology of post-inflammatory gastrointestinal (GI) motility dysfunction, after resolution of acute symptoms of inflammatory bowel diseases (IBD) and intestinal infection, is largely unknown. Here, using an established mouse model of experimental enteritis, we show that enhancement of smooth muscle cell (SMC) contraction by interleukin (IL)-17A may be involved in postinflammatory GI hypermotility. To examine the effect of IL-17 in the small intestinal smooth muscle, we used whole genome microarray expression profiling to find out the genes which respond to IL-17 stimulus. The smooth muscle strips were peeled off from mouse small intestine and incubated 24h with or without IL-17. And we also examined the effect of 6-shogaol, which is one of the ingredients of Japanese traditional medicine for intestinal mortor disorder, Daikenchuto, in IL-17 stimulated small intestinal smooth muscle strip.
2012-09-15 | GSE39573 | GEO
Project description:Genome scale expression data on absolute numbers of gene isoforms offer essential clues for cellular functions and biological processes. Gastrointestinal (GI) motility is regulated by smooth muscle cells (SMC) closely contacted with interstitial cells of Cajal (ICC) and fibroblast-like PDGFRα+ cells (PαC), forming an electrical syncytium. To uncover genetic identifies and cellular functions of the cells, we isolated these three cell populations from mouse small intestine and colon, obtained the transcriptome for each type of cells, and built each cell type transcriptome browser. To our knowledge, this is the first genetic resource providing a comprehensive reference for all mRNA transcripts expressed in these unique GI cell populations. Integration of these data with the UCSC genome browser revealed novel cell-specific markers, ion channel and transporter isoforms, and unique cellular and biological functions of these cells in GI physiology. Our transcriptome browsers bring new insight into the alternative expression of genes in different types of the cells and provides references for future functional studies.
2015-07-31 | GSE57776 | GEO
Project description:The enteric nervous system (ENS) and SIP (Smooth muscle cells-Interstitial cells of Cajal-PDGFRα+ cells) syncytium play an important role in controlling gastrointestinal motility. This study aimed to investigate the dynamic regulatory mechanisms of the ENS-SIP system on colon motility during postnatal development. Colonic samples of postnatal 1 week (PW1), PW3, and PW5 old murine were characterized by RNA sequencing, qRT-PCR, and immunoblotting. The current study showed that ENS and glial cells including ICCs and PDGFRα+ cells become increasingly mature in both the postnatal proximal and distal colon. The transcriptional expression of Pdgfrα, c-Kit, P2ry1, Nos1, and Slc18a3, and the protein expression of nNOS, c-Kit, and ANO1 significantly increased with age. In conclusion, during postnatal development, molecular data demonstrated the gradual maturation of ICC and PDGFRα+ cells, including nitrergic and cholinergic nerves and purinergic receptors. Our findings are important in understanding the role of ENS and interstitial cells with specific receptors for the generation of mature colonic migrating motor complexes in young murine colons.
2024-01-03 | GSE186568 | GEO
Project description:Introduction: Type 1 diabetes (T1D) significantly affects gastrointestinal (GI) motility and contributes to complications, such as gastroparesis, constipation, and fecal incontinence. Notably, these complications have a higher prevalence in female patients, underscoring a critical knowledge gap in the understanding of the underlying mechanisms. Given the emerging role of the G-protein-coupled estrogen receptor (GPER) in GI motility regulation, our study investigated the potential contribution of diabetes-induced changes in GPER expression to pathophysiology. Hypothesis: We hypothesized that diabetes-induced perturbations in GPER expression contribute to pathophysiological mechanisms affecting GI motility in T1D, with notable sex-dependent variations. Methods: we assessed GPER mRNA and protein expression levels using quantitative reverse-transcription PCR and western blot analyses, and quantified the changes in nuclear DNA methyltransferases and histone modifications (H3K4Me3, H3Ac, and H3K27Ac) were quantified using ELISA kits. Targeted bisulfite and chromatin immunoprecipitation sequencing were used to evaluate DNA methylation and histone modifications around the GPER promoter by chromatin immunoprecipitation assays in gastric and colonic smooth muscle tissues of male and female control (CTR) and non-obese diabetic (NOD) mice. Results: Our results revealed significant downregulation of GPER in NOD mice, with marked sex-dependent variations. Mechanistically, this downregulation was associated with reduced H3K4me3, H3ac, and H3K27ac levels in NOD male gastric smooth muscle. In contrast, downregulation in female gastric smooth muscle cells has been linked to decreased H3K4me3 and H3ac levels. Male NOD colonic smooth muscle exhibited elevated H3ac and H3K27ac levels, whereas female NOD colonic smooth muscle demonstrated diminished enrichment of H3ac and H3K27ac at the GPER promoter. Additionally, DNA methylation is elevated in NOD male colonic smooth muscle compared to NOD females. Conclusion: Our findings elucidate sex-specific epigenetic mechanisms contributing to T1D-mediated suppression of GPER expression in the gastrointestinal tract. These insights not only advance our understanding of T1D complications but also suggest promising avenues for targeted therapeutic interventions.
2024-05-29 | GSE255236 | GEO
Project description:Previous efforts to conditionally delete the Srf transcription factor in smooth muscle lineages were met with early demise of the mouse due to a gastrointestinal (GI) obstruction phenotype. We have developed a new, more VSMC selective Cre recombinase mouse (Itga8-CreERT2), that circumvents the GI phenotype thus affording the opportunity to evaluate, in an unambiguous manner, VSMC phenotypes where Srf is reduced. The mice live for at least 6 months post-tamoxifen and here we report the first RNA-seq experiments in mouse aortic SMC where Srf is reduced.
2020-04-18 | GSE138824 | GEO