Project description:The left atrium consists of three major parts: the peri-pulmonary vein portion, the appendage, and the vestibule. Previous transcriptional profiling of the adult left atrium and identification of the Tbx5-dependent transcriptome has focused on the atrial appendage (Nadadur et al 2016, Science Translational Medicine). In that study, Tbx5 was shown to regulate a gene regulatory network of atrial identity in the appendage and in its absence results in atrial fibrillation. In order to investigate the regional differences in the transcriptome of the left atrium, the left atrial appendage and the peri-pulmonary vein portion from adult mice were compared by RNA-sequencing. Additionally, as Tbx5 is major regulator of atrial identity, the peri-pulmonary vein portion of the atria was likewise examined following removal of Tbx5 using an adult specific conditional knockout of Tbx5.
Project description:Regional differential expression of atrial fibrillation risk genes in the left atrium and pulmonary veins is not well studied, but may yield insights into atrial fibrillation pathogenesis. We tested the hypothesis that there is significant regional differential expression in left atrium structures. RNAseq was performed in 25 regions within the pulmonary veins (n=12), left atrial body (n=10), and left atrial appendage (n=3) from a 75 year old male with hypertension and atrial fibrillation who died of a stroke. These data show that genes involved in atrial fibrillation pathogenesis have substantial regional expression heterogeneity, particularly when comparing the left atrial body, pulmonary veins and left atrial appendage.
Project description:We report the application of a pericentriolar material 1 (PCM-1) based cardiomyocyte-specific nuclear isolation protocol on human cardiac tissue to specifically ask what transcriptional changes occur in cardiomyocytes of humans with atrial fibrillation. We performed RNA-sequencing on the cardiomyocyte-specific nuclear RNA and found that there are more differentially dysregulated (1343) than similarly regulated transcripts (99) in the right versus left atria. This study is the first of its kind aimed at understanding the transcriptional changes that occur specifically in the left and right atrial cardiomyocytes of humans with atrial fibrillation.
Project description:Single-nucleus RNA sequencing (snRNA-seq) was used to profile the transcriptome of 16,015 nuclei in human adult testis. This dataset includes five samples from two different individuals. This dataset is part of a larger evolutionary study of adult testis at the single-nucleus level (97,521 single-nuclei in total) across mammals including 10 representatives of the three main mammalian lineages: human, chimpanzee, bonobo, gorilla, gibbon, rhesus macaque, marmoset, mouse (placental mammals); grey short-tailed opossum (marsupials); and platypus (egg-laying monotremes). Corresponding data were generated for a bird (red junglefowl, the progenitor of domestic chicken), to be used as an evolutionary outgroup.
Project description:Atrial fibrillation (AF) is the most common persistent arrhythmia that affect 1–2% of the general population. People with AF display an array of complications cardiogenic stroke and systemic embolism caused by hemodynamic instability and blood hypercoagulability in clinical practice. However, it’s still unclear whether and how ubiquitylated proteins react to AF in the left atrial appendage of patients with AF and valvular heart disease. This theory focuses on the changes of ubiquitylated proteins in atrial fibrillation associated with heart valve disease. We firstly widely analysis the proteins ubiquitination in patients with atrial fibrillation.
Project description:Background: Atrial fibrillation (AF) causes atrial remodeling, and the left atrium (LA) is the favored substrate for maintaining AF. However, it remains unclear if AF remodels both atria differently and contributes to LA arrhythmogenesis and thrombogenesis. Results: AF was associated with differential LA-to-RA gene expression related to specific ion channels and pathways as well as upregulation of thrombogenesis-related genes in the LA appendage. Targeting the molecular mechanisms underlying the LA-to-RA difference and AF-related remodeling in the LA appendage may help provide new therapeutic options in treating AF and preventing thromboembolism in AF. Paired left atrial and right atrial specimens were obtained from 13 patients with persistent AF receiving valvular surgery. The Paired specimens were sent for microarray comparison. Selected results were validated by quantitative real time-PCR (q-PCR) and Western blotting. Ultrastructural changes in the atria were evaluated by immunohistochemistry.
