Calcium-dependent regulation of physiological vs pathological cardiomyocyte hypertrophy.

Cardiomyocyte hypertrophic growth contributes to the adaptative response of the heart to meet sustained increases in hemodynamic demand. While hypertrophic responses to physiological cues maintains or enhances cardiac function, when triggered by pathological cues, this response is maladaptive, associated with compromised heart function, although initially, this response maybe adaptive with preserved function. Since cues and activated pathways associated with both forms of hypertrophy overlap, the question arises as to the mechanism that determines these different outcomes.

Benchmarking of computational demultiplexing methods for single-nucleus RNA sequencing data.

Single-nucleus RNA sequencing (snRNA-Seq) has transformed our understanding of complex tissues, providing insights into cellular composition and heterogeneity in gene expression between cells, and their alterations in development and disease. High costs however constrain the number of samples analysed. Sample pooling and their demultiplexing following sequencing based on prior labelling with antibodies or lipid anchors conjugated to DNA barcodes (cell hashing and MULTI-seq), or using genetic differences between samples, provides a solution.

Small-molecule-induced ERBB4 activation to treat heart failure.

Heart failure is a common and deadly disease requiring new treatments. The neuregulin-1/ERBB4 pathway offers cardioprotective benefits, but using recombinant neuregulin-1 as therapy has limitations due to the need for intravenous delivery and lack of receptor specificity. We hypothesize that small-molecule activation of ERBB4 could protect against heart damage and fibrosis.

Precision sampling of discrete sites identified during in-vivo functional testing in the mammalian heart.

Ventricular arrhythmias after myocardial infarction (MI) originate from discrete areas within the MI border zone (BZ), identified during functional electrophysiology tests. Accurate sampling of arrhythmogenic sites for ex-vivo study remains challenging, yet is critical to identify their tissue, cellular and molecular signature. In this study, we developed, validated, and applied a targeted sampling methodology based on individualized 3D prints of the human-sized pig heart.