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Gene expression profile at single cell level of non-myocytic cells of the heart (NCM) from TRPM4 WT and KO mice 24h or 72h after SHAM intervention or LAD ligation

ABSTRACT: Many different cell types constitute the heterogenous group of non-cardiomyocytes (NCM) of the heart. We used single cell RNA sequencing (scRNA-seq) to analyze the diversity of NCM and especially how the absence of TRPM4 affects the inflammatory response post myocardial infarction.

ORGANISM(S): Mus musculus

PROVIDER: GSE210159 | GEO | 2023/02/15

REPOSITORIES: GEO

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Gene expression profile at single cell level of non-myocytic cells of the heart (NCM) from TRPM4 WT and KO mice 24h or 72h after SHAM intervention or LAD ligation

Project description:Gene expression profile at single cell level of non-myocytic cells of the heart (NCM) from TRPM4 WT and KO mice 24h or 72h after SHAM intervention or LAD ligation

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Myocardial Infarction accelerates breast cancer progression via innate immune reprogramming (RNA-seq: sham vs LAD ligation)

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Myocardial Infarction accelerates breast cancer progression via innate immune reprogramming (RNA-seq: sham vs LAD ligation)

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RNA-sequencing of WT and P2Y4 KO pericardial adipose tissue (PAT) 24 hours after left anterior descending artery (LAD) ligation

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Gene expression profile at bulk (24h, 48h & 72h) and single nucleus (24h) level of mouse right kidney post sham operation and unilateral nephrectomy.

Project description:The mechanism driving the remarkable ability of the remaining kidney to enlarge and increase its function following removal of its contralateral pair remains elusive. To explore the pathways driving compensatory renal hypertrophy, comprehensive RNA-seq transcriptional studies in the kidneys of mice undergoing hypertrophy 24, 48 and 72 hours following nephrectomy have been undertaken and compared with mice undergoing sham operations. The results reveal substantial time dependent enhancement of cholesterol biosynthesis pathways, increases in mitochondrial gene expression and cell cycle perturbations. Single nuclei RNA-Seq 24 hours post nephrectomy was used to further explore cholesterol biosynthesis signature and its driver SREBP2. In a cell specific manner, snRNA-seq demonstrated that SREBP2 activity increases in proximal tubules and medullary thick ascending limb and is responsible for cell size regulation following IGF-1 stimulation. These results suggest a previously undescribed role for SREBP2 in the mechanism underlying compensatory renal hypertrophy. This mechanism might be amenable to therapeutic manipulation to enhance kidney size and function.

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Transcriptional profile of PDGFRa+ Sca-1+ and Sca-1- cells at steady state and at 7, 14 and 28 days post LAD ligation

Project description:The cardiac stroma contains multipotent mesenchymal progenitors. However, lineage relationships within cardiac stromal cells are poorly defined. Here, we identify heart-resident PDGFRa+ SCA-1+ cells as cardiac Fibro/Adipogenic Progenitors (cFAPs) and show that they respond to ischemic damage by generating SCA-1- fibrogenic cells. Pharmacological blockade of this differentiation step with an anti-fibrotic tyrosine kinase inhibitor decreases post-myocardial infarction (MI) remodeling and leads to improvement in heart function.

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Trpm4-induced gene expression changes in Th1 and Th2 cells

Project description:T helper cell subsets have unique calcium (Ca2+) signals when activated with identical stimuli. The regulation of these Ca2+ signals and their correlation to the biological function of each T cell subset remains unclear. Trpm4 is a Ca2+-activated cation channel that we found is expressed at higher levels in Th2 cells compared to Th1 cells. Inhibition of Trpm4 expression increased Ca2+ influx and oscillatory levels in Th2 cells and decreased influx and oscillations in Th1 cells. This inhibition of Trpm4 expression also significantly altered T cell cytokine production and motility. Our experiments revealed that decreasing Trpm4 levels divergently regulates nuclear localization of NFAT. Consistent with this, gene profiling did not show Trpm4 dependent transcriptional regulation and T-bet and GATA-3 levels remain identical. Thus, Trpm4 is expressed at different levels on T helper cells and plays a distinctive role in T cell function by differentially regulating Ca2+ signaling and NFAT localization. T helper cell gene expression levels when Trpm4 is inhibited by siRNA or dominant negative Trpm4 construct. The ion channel Trpm4 was inhibited in Th1 or Th2 cells using either siRNA or a dominant negative Trpm4 retrovirus and changes in gene profiles were analyzed.

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Comparison of transient and permanent LAD ligation in mice using 18F-FDG PET imaging.

Project description:ObjectiveAnimal models for myocardial injuries represent important cornerstones in cardiovascular research to monitor the pathological processes and therapeutic approaches. We investigated the association of 18F-FDG derived left ventricular metabolic volume (LVMV), defect area and cardiac function in mice after permanent or transient ligation of the left anterior descending artery (LAD).MethodsSerial non-invasive ECG-gated 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (18F-FDG PET) after permanent or transient LAD ligation enabled a longitudinal in vivo correlation of 18F-FDG derived left ventricular metabolic volume to functional parameters and myocardial defect.ResultsThe LVMV shows a more prominent drop after permanent than transient LAD ligation and recovers after 30 days. The loss of LVMV correlates with the defect area assessed by QPS software. Cardiac function parameters (e.g., EDV, ESV, SV) by the QGS software positively correlate with LVMV after permanent and transient LAD ligation.ConclusionsThis study provides novel insight into 18F-FDG derived LVMV after permanent and transient LAD ligation by longitudinal in 18F-FDG PET imaging and underlines the associations of the FDG derived parameter and cardiac function.

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renal ischemia vs sham - 24h

Project description:This experiment was designed to determine alterations in gene expression in rat kidney following ischemia reperfusion injury. Several genes were identified that were significantly up regulated in kidneys at 24 hours following a 45 min ischemic injury. This group comprises data from 4 different hybridizastion deriving from 4 pairs of animals (1 sham vs 1 ischemic animal) per hybridization Keywords: disease state

2007-08-15 | GSE6748 | GEO

Plasma metabonomics study on Chinese medicine syndrome evolution of heart failure rats caused by LAD ligation.

Project description:BackgroundChinese medicine syndromes (Zheng) in many disease models are not clearly characterized or validated, and the concepts of Chinese medicine syndromes are confounding and controversial. Metabonomics has been applied to the evaluation and classification of the Chinese medicine syndromes both in clinical and nonclinical studies. In this study, we aim to investigate the evolution of the Chinese medicine syndrome in myocardial infarction induced heart failure and to confirm the feasibility of the Zheng classification by plasma metabonomics in a syndrome and disease combination animal model.MethodsThe heart failure (HF) model was induced by ligation of the left anterior descending coronary artery (LAD) in Sprague-Dawley rats. The rats were divided into the following two groups: the HF model group (LAD ligation) and the sham operated group. GC-MS was used with pattern recognition technology and principal component analysis (PCA) to analyze the plasma samples at 4, 21 and 45 day after operation.ResultsIt was determined that the period from 7 to 28 days was the stable time window of ischemic heart failure with qi deficiency and blood stasis syndrome (QDBS), and the qi deficiency syndrome occurred at 1 to 4 days and 45 to 60 days after operation. The results exhibited 5 plasma metabolite changes in the same trend at 4 and 21 day after the LAD operation, 7 at 21 and 45 day, and 2 at 4 and 45 day. No metabolite showed the same change at all of the 3 time points. At day 21 (the QDBS syndrome time point) after operation, 4 plasma metabolites showed the same trends with the results of our previous study on patients with the blood stasis syndrome.ConclusionsThe syndrome diagnosis is reliable in the HF rat model in this study. Plasma metabolites can provide a basis for the evaluation of Chinese medicine syndrome animal models.

| S-EPMC4227006 | biostudies-literature

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