Project description:Myocarditis is a heart condition that causes inflammation and results in the loss of heart muscle cells, often leading to fibrosis (scarring) of the heart tissue and heart failure. However, the molecular mechanisms underlying immune cell control and maintenance of tissue integrity in the inflamed cardiac microenvironment remain elusive. Based on our finding that bone morphogenic protein-4 (BMP4) serum concentration was reduced in myocarditis patients in combination with comprehensive single cell and single nucleus RNA sequencing analyses of inflamed murine and human myocardial tissue indicated that BMP4 gradients maintain cardiac tissue homeostasis. Indeed, restoration of BMP signaling through antibody-mediated neutralization of the BMP-inhibitors GREM1 and GREM2 reduced CD4+ T cell-mediated myocardial inflammation and blocked disease progression by reduction of adverse fibrotic remodelling. These results unveil a key function of the BMP4-GREM1/2 axis as promising approach for treating myocardial inflammation and the serious complications of cardiac fibrosis and heart failure.
Project description:We performed single-nucleus RNA-seq on subcutaneous adipose tissue biopsies of 68 participants from the Roux-en-Y versus one-anastomosis gastric bypass (RYSA) cohort.
Project description:Single-nucleus RNA-seq was performed to characterize the transcriptomes of cell types in human subcutaneous adipose tissue. Biopsies from 16 Finnish participants from the Finnish Twin Study and CRYO study were included.
Project description:Primary carnitine deficiency (PCD) is an autosomal recessive disorder caused by mutations in the gene SLC22A5, encoding for the plasmalemmal carnitine transporter OCTN2. PCD patients suffer from muscular weakness and dilated cardiomyopathy (DCM). However, currently available PCD models were unable to distinguish causative from secondary pathomechanisms. To further understand the contribution of cellular subclusters to the PCD disease phenotype we analyzed engineered heart tissues from OCTN2-defective genotype in comparison to isogenic control using single-nucleus RNA sequencing.