Gut HIF2α signaling is increased after VSG, and gut activation of HIF2α decreases weight, improves glucose, and increases GLP-1 secretion
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ABSTRACT:
PROVIDER: PRJNA716525 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the SubSeries listed below.
2022-02-03 | GSE169403 | GEO
Project description:Gut intraepithelial lymphocytes (IELs) are one of the few immune cell populations in the body that expresses glucagon-like 1 receptors (GLP-1R). To test the potential effects of GLP-1 on the gut microbiota through the gut IEL GLP-1R, we performed 16s rRNA seq on the DNA isolated from the fecal pellet of Lck-Cre; Glp1rfl/fl mice (Glp1rTcell-/-) or controls (Glp1rTcell+/+) fed a high-fat diet (HFD) for 12 weeks followed by 1 week of HFD plus semaglutide (10 ug/kg) or vehicle treatment. Fecal pellets from a group of age-matched, sex-matched control mice were included as a chow control group.
2022-08-29 | GSE202452 | GEO
Project description:Using a combination of single-cell RNAseq methods and murine pulmonary hypertension models, we show HIF2α overexpressing pericytes’ transformation into SMC-like cells, confirming HIF2α as a major molecular regulator in hypoxia-induced pulmonary hypertension (PH) and vascular remodeling. We demonstrate that HIF2α overexpression in pericyte-dominant transgenic mice exacerbates PH and right ventricular hypertrophy (RVH), whereas disruption of HIF2α expression attenuates the development of PH.
2024-08-25 | GSE211985 | GEO
Project description:To investigate the effect of vertical sleeve gastrectomy (VSG) on intestinal stem cell (ISC)/progenitor cells, we performed VSG on a dietary-induced obese mouse models that expresses eGFP fluorescence tag in its Lgr5 gene, a specific marker of ISCs. We then performed RNAseq on the GFP-positive ISCs sorted from the duodenal, jejunal, and ileal epithelia. We pre-sorted immune cells (CD45 positive), endothelial cells (CD31 positive), apoptotic (Annexin5 positive), and dead cells (stained with Sytox blue). By performing differential expression analysis (P < 0.05, adjusted P <0.2, log2 fold change > 0.5, normalized count > 50 by DESeq2), we found that VSG altered 467 genes (259 up; 208 down) in the duodenum, 510 genes (348 up; 162 down) in the jejunum, and 955 genes (600 up; 355 down) in the ileum. Of note, some of the VSG-increased genes are region-specific. Overall, our data suggest that VSG induces ISC fate toward enteroendocrine cell differentiation and that there are critical regional differences among ISCs in the duodenum, jejunum, and ileum.
2022-06-29 | GSE173465 | GEO
Project description:Background: in clear cell renal cell carcinoma (ccRCC), 80% of cases have biallelic inactivation of VHL gene, leading to constitutive activation of both HIF1α and HIF2α. As HIF2α is the driver of the disease promoting tumour growth and metastasis, drugs targeting HIF2α have been developed. However, resistance is common, therefore new therapies are needed. Methods: we generated the 786-0 HIF2α knockout (KO) cell line and assessed the HIF2α antagonist PT2385 in several steps of tumour development. RNA sequencing was performed to identify genes differentially expressed between them and a drug screening was used to identify drugs with differential effects on HIF2α-expressing and KO cells. Results: HIF2α KO promoted cell migration, reduced proliferation and clonogenicity, as well as metastasis, whereas PT2385 treatment only inhibited tumour cell invasion. There was a large set of co-ordinately regulated genes, but HIF2α KO cells also had up-regulation of genes related to EMT and downregulation of genes involving cell migration and extracellular matrix. The HIF2α KO increased sensitivity to statins, while PT2385 had no effect. Conclusions: this study shows new pathways that could be targeted combined with PT2385 to enhance its therapeutic effects and delay resistance.
2021-08-11 | GSE153711 | GEO
Project description:Gut intraepithelial lymphocytes (IELs) are one of the few immune cell populations in the body that expresses glucagon-like 1 receptors (GLP-1R). To test the potential effects of GLP-1 on gut IEL function, we performed bulk RNA-seq on gut IELs isolated from C57BL/6J mice treated with anti-CD3 and with or without exendin-4 for 3 hours.
2022-08-29 | GSE202453 | GEO
Project description:As an additional strategy for investigating T. brucei transcriptome responsiveness, the mRNA of a highly important protein, the variant surface glycoprotein (VSG) the major surface protein in the bloodstream stage, was suppressed with RNAi. VSG RNAi results in arrest of cell cycle progression in the bloodstream stage. In addition, the mRNA of a highly important protein for endocytosis, the clathrin heavy chain (CLH), was suppressed with RNAi. CLH knockdown leads to a complete block to endocytosis. We hypothesized that if trypanosomes were able to sense alterations in trafficking and respond to these changes, then depletion of these ORFs by RNAi would be expected to elicit a response at the transcriptome level.<br> <br> part 1: 2 biological replicates of SMB cells transfected with the VSG- RNAi vector grown under normal conditions (non-induced), and 2 replicates of the same cells treated with 1 ug/ml tetracycline (induced) for 24hr, as well as dye swaps were used.<br> <br> part 2: 2 biological replicates of SMB cells transfected with the VSG- RNAi vector grown under normal conditions (non-induced), and 2 replicates of the same cells treated with 1 ug/ml tetracycline (induced) for 3 days, as well as dye swaps were used.<br> <br> part 3: 3 biological replicates of SMB cells transfected with the CLH- RNAi vector grown under normal conditions (non-induced), and 3 replicates of the same cells treated with 1 ug/ml tetracycline (induced), as well as dye swaps were used.
2008-06-26 | E-MEXP-1528 | biostudies-arrayexpress
Project description:Vascular remodeling is the process of structural alteration and cell rearrangement of blood vessels in response to injury and is the cause of many of the world's most afflicted cardiovascular conditions, including pulmonary arterial hypertension(PAH). Many studies have focused on the effects of vascular endothelial cells and smooth muscle cells(SMCs) during vascular remodeling, but pericytes, an indispensable cell population residing largely in capillaries, are ignored in this maladaptive process. Here we report that hypoxia-inducible factor 2α(HIF2α) expression is increased in human PAH patient lung tissues and HIF2α overexpressed pericytes result in greater contractility and an impaired endothelial-pericyte interaction. Using single-cell RNAseq and hypoxia-induced pulmonary hypertension(PH) models, we show HIF2α as a major molecular regulator for pericytes’ transformation into SMC-like cells. HIF2α overexpression in pericyte-selective mice exacerbate PH and right ventricular hypertrophy. Temporal cellular lineage tracing shows that HIF2α overexpressing reporter NG2+ cells (pericyte-selective) relocate from capillaries to arterioles and co-express SMA. This novel insight into the potential role of NG2+ pericytes in pulmonary vascular remodeling via HIF2α signaling suggests a potential drug target for PH.
2023-12-11 | GSE249461 | GEO
Project description:Trypanosoma brucei is a protozoan parasite that causes human African trypanosomiasis. Its major surface antigen VSG is expressed from subtelomeric loci in a strictly monoallelic manner. We previously showed that the telomere protein TbRAP1 binds dsDNA through its 737RKRRR741 patch to silence VSGs globally. How TbRAP1 permits transcription of the single active VSG is unknown. Through NMR structural analysis, we unexpectedly identify an RNA Recognition Motif (RRM) in TbRAP1, which is unprecedented for RAP1 homologs. Assisted by the 737RKRRR741 patch, TbRAP1 RRM recognizes consensus sequences of VSG 3’UTRs in vitro and binds the active VSG RNA in vivo. Mutating conserved RRM residues abolishes the RNA binding activity, significantly decreases the active VSG RNA level, and derepresses silent VSGs. The competition between TbRAP1’s RNA and dsDNA binding activities suggests a novel mechanism of monoallelic expression, in which the active VSG’s abundant RNA antagonizes TbRAP1’s silencing effect, thereby sustaining its full-level transcription.
2023-02-17 | GSE193394 | GEO
Project description:Glucagon-like peptide-1 (GLP-1) is an incretin hormone that potentiates glucose stimulated insulin secretion. GLP-1 is classically produced by gut L cells; however, under certain circumstances alpha-cells can express the prohormone convertase required for proglucagon processing to GLP-1, prohormone convertase 1/3 (PC1/3), and can produce GLP-1. However, the mechanisms through which this occurs are poorly defined. Understanding the mechanisms by which alpha-cell PC1/3 expression can be activated may reveal new targets for diabetes treatment. Here, we demonstrate that the GLP-1 receptor (GLP-1R) agonist, liraglutide, increases alpha-cell GLP-1 expression in a beta cell GLP-1R-dependent manner. We demonstrate that this effect of liraglutide is translationally relevant in human islets through application of a new scRNA-sequencing technology, DART-seq. We find that the effect of liraglutide to increase alpha-cell PC1/3 mRNA expression occurs in a sub-cluster of alpha-cells and is associated with increased expression of other beta-cell-like genes, which we confirm by IHC. Finally, we find that the effect of liraglutide to increase bi-hormonal insulin+ glucagon+ cells is mediated by the beta-cell GLP-1R in mice. Together, our data validate a new high-sensitivity method for scRNA-sequencing in human islets and identify a novel GLP-1 mediated pathway regulating human alpha-cell function.
2020-12-24 | GSE163744 | GEO