Cellular Atlas of Human Heart Failure
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA762100 | ENA |
REPOSITORIES: ENA
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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.
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Project description:Pathological cardiac hypertrophy is a leading cause of heart failure. The understanding of disease mechanisms is primarily based on experimental models, but knowledge of the full repertoire of cardiac cells and their gene expression profiles in the human heart is missing. Here, using large-scale single-nucleus transcriptomes, we highlight the transcriptional response of cardiomyocytes to pressure overload in humans with stenosis of the aortic valve and disclose major alterations in cellular cross-talk. Cardiomyocytes showed a reduction of incoming connections with endothelial cells and fibroblasts. Particularly Eph receptor tyrosine kinases, including the predominant EPHB1 gene, were significantly down-regulated in cardiomyocytes of the hypertrophied heart. We compared 5 AS patients to healthy patients from the human heart cell ATLAS (https://www.heartcellatlas.org). This repository contains the processed files from the single nuclei RNA-SEQ.
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Project description:MS analysis of human cardiac samples from left ventricles of patients undergoing cardiac transplantation due to ischaemic heart failure (n=5) or non-ischaemic heart failure (n=10), as well as controls samples (n=6). Analysis of extracellular matrix protein enriched extracts.
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Project description:MS analysis of human cardiac samples from left ventricles of patients undergoing cardiac transplantation due to ischaemic heart failure (n=5) or non-ischaemic heart failure (n=10), as well as controls samples (n=6). Analysis of extracellular matrix protein enriched extracts.
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Project description:The microtubule (MT) cytoskeleton can provide a mechanical resistance that can impede the motion of contracting cardiomyocytes. Yet a role of the MT network in human heart failure is unexplored. Here we utilize mass spectrometry to characterize changes to the cytoskeleton in human heart failure. Proteomic analysis of left ventricle tissue reveals a consistent upregulation and stabilization of intermediate filaments and MTs in human heart failure. This dataset includes left ventricular (LV) myocardium from 34 human hearts – either non-failing (NF) or failing hearts. NF hearts are subdivided into normal or compensated hypertrophy (cHyp), while failing hearts are subdivided into ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM), and hypertrophic cardiomyopathy with preserved or reduced ejection fraction (HCMpEF and HCMrEF, respectively). Further details on patient classification and in vivo parameters on each heart are listed in sample details.txt.
2018-06-06 | PXD008934 | Pride
Project description:The goal of this study is to compare the transcriptome of heart failure patients (with ischemic or dilated cardiomyopathy) undergoing heart transplantation compared with healthy controls. We analyzed 36 human samples. 13 from ischemic and 13 from dilated human hearts compared with 10 healthy control donors.
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Project description:MS analysis of human cardiac samples from left ventricles of patients undergoing cardiac transplantation due to ischaemic heart failure. Analysis of extracellular matrix enriched extracts.
2021-12-15 | PXD024135 | Pride