Project description:Heart failure represents a major cause of morbidity and mortality worldwide. Single cell transcriptomics have revolutionized our understanding of cell composition and associated gene expression across human tissues. Through integrated analysis of single cell and single nucleus RNA sequencing data generated from 45 individuals, we define the cell composition of the healthy and failing human heart. We identify cell specific transcriptional signatures of heart failure and reveal the emergence of disease associated cell states. Intriguingly, cardiomyocytes converge towards a common disease associated cell state, while fibroblasts and myeloid cells undergo dramatic diversification. Endothelial cells and pericytes display global transcriptional shifts without changes in cell complexity. Collectively, our findings provide a comprehensive analysis of the cellular and transcriptomic landscape of human heart failure, identify cell type specific transcriptional programs and states associated with disease, and establish a valuable resource for the investigation of human heart failure.
Project description:The goal of this dataset was to use RNA-seq in human heart tissue to delineate etiology-specific gene expression signatures in heart failure.
Project description:Background. Chronic Heart Failure (CHF) is a systemic syndrome with a poor prognosis and a need for novel therapies. We investigated whether whole-blood transcriptomic profiling can provide new mechanistic insights into CHF. Baseline whole-blood transcriptome profiles were generated from 944 CHF patients from the BIOSTAT-CHF Study.
Project description:We have utilized the RNA-Seq technology to identify genes with distinct expression patterns between failing and non-failing hearts. In an era of next-generation sequencing studies, our study demonstrates how knowledge gained from a small set of samples with accurately measured gene expressions using RNA-Seq can be leveraged as a complementary strategy to discern the genetics of complex disorders. Identify the signature genes based on RNA-seq come from six Heart Failure and healthy individuals. Validation is based on Affymetrix microarray of a total of 313 individuals with/without Heart Failure.
Project description:Heart failure is the final stage of various cardiovascular diseases, which seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including RNA binding protein RBFox2. It participates in regulation of cardiac function in multiple aspects and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures including mRNAs as well as miRNAs in the mouse model of heart failure after TAC surgery. Global and association analyses revealed that large-scale upregulation of miRNAs occurred at heart failure, which was not only responsible for degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBfox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBfox2 was targeted by multiple miRNAs including let-7, mir-16 and mir-208b, which were critical for cardiac function and upregulated in heart failure stage. Overexpression of these miRNAs suppressed rbfox2 protein and its downstream effects in cardiomyocytes, evidenced by suppressed alternative splicing of Enah gene and impaired E-C coupling via repression of Jph2 protein. Inhibition of let-7, the most abundant of these miRNAs in the heart, could rescue Rbfox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. These findings not only revealed the mechanism leading to RBFox2 depression in heart failure, but also provided an approach to rescue RBFox2 by miRNAs inhibition for the treatment of heart failure.
Project description:Heart failure is the final stage of various cardiovascular diseases, which seriously threatens human health. Increasing mediators have been found to be involved in the pathogenesis of heart failure, including RNA binding protein RBFox2. It participates in regulation of cardiac function in multiple aspects and plays a critical role in the process of heart failure. However, how RBFox2 itself is regulated remains unclear. Here, we dissected transcriptomic signatures including mRNAs as well as miRNAs in the mouse model of heart failure after TAC surgery. Global and association analyses revealed that large-scale upregulation of miRNAs occurred at heart failure, which was not only responsible for degradation of numerous mRNA transcripts, but also suppressed the translation of key proteins such as RBfox2. With the aid of Ago2 CLIP-seq data, luciferase assays verified that RBfox2 was targeted by multiple miRNAs including let-7, mir-16 and mir-208b, which were critical for cardiac function and upregulated in heart failure stage. Overexpression of these miRNAs suppressed rbfox2 protein and its downstream effects in cardiomyocytes, evidenced by suppressed alternative splicing of Enah gene and impaired E-C coupling via repression of Jph2 protein. Inhibition of let-7, the most abundant of these miRNAs in the heart, could rescue Rbfox2 protein as well as its downstream effects in dysfunctional cardiomyocytes induced by ISO treatment. These findings not only revealed the mechanism leading to RBFox2 depression in heart failure, but also provided an approach to rescue RBFox2 by miRNAs inhibition for the treatment of heart failure.
Project description:The aim of the study was to identify genes which are differentially expressed in the blood of dogs suffering from heart failure (HF) in comparison to healthy control dogs. The dogs with HF were categorized according to the ISACHC classification system (International Small Animal Cardiac Health Council). RNA from healthy dogs and dogs with different stages of heart failure were hybridized to Agilent two color microarrays with a common reference.