Biology subjects

Rog-Zielinska, E.

Publications and source records attributed to Rog-Zielinska, E..

3 recordsLinked to original sources

bioRxiv2024

Atrial Granules in Atrial Cardiomyocytes as Acidic Calcium Stores

Acidic calcium stores significantly influence basal calcium transient amplitude and {beta}-adrenergic responses in cardiomyocytes. Atrial myocytes express a small acidic organelle called atrial granules (AG), which store and excrete atrial natriuretic peptide and are not expressed by healthy ventricular myocytes. AG are known to be acidic with a high calcium content. The number and position of these calcium-rich organelles relative to other signaling sites has not been investigated. Staining of acidic organelles in adult guinea pig cardiomyocytes showed the presence of fluorescent acidic puncta throughout the cytosol. Atrial myocytes exhibited an increased concentration of acidic organelles at the nuclear poles. Live cell fluorescent studies using PBA to inhibit peptidylglycine -amidating monooxygenase, a crucial component of AG membranes, effectively eliminated staining at the nuclear poles and most acidic puncta in atrial cells. The application of PBA to ventricular myocytes did not affect LysoTracker staining. Electron microscopy studies on goat atrial fibrillation (AF) and sham control tissue, allowed visualization of AGs. Quantitative analysis revealed AGs to be in close apposition to the sarcoplasmic reticulum and mitochondria. AGs were significantly increased in AF goat samples when compared to sinus rhythm from 3D electron tomography images. Our imaging studies suggest that AGs make up a large percentage of atrial acidic stores, with AG associated with the sarcoplasmic reticulum and their number increasing during AF. We raise the question whether the positioning of AGs are strategic to communicate with other calcium organelles. Further studies to investigate whether AGs contribute to physiological calcium signalling are required.

physiology↗

bioRxiv2024

Spatio-temporal dynamics of the fibrotic niche in cardiac repair

The heart is one of the least regenerative organs in humans, and ischemic heart disease is the leading cause of death worldwide. Understanding the cellular and molecular processes that occur during cardiac wound healing is an essential prerequisite to reducing health burden and improve cardiac function after myocardial tissue damage. By integrating single-cell RNA-sequencing with imaging-based spatial transcriptomics, we reconstructed the spatio-temporal dynamics of the fibrotic niche after ventricular injury in adult mice. Our analysis reveals dynamic regulation of local cell communication niches over time. We identified interactions that regulate cardiac repair, including fibroblast proliferation silencing by Trem2high macrophages that prevents excessive fibrosis. Moreover, we discovered a rare population of dedifferentiating cardiomyocytes during early post-lesion stages, which was sustained by signals from myeloid and lymphoid cells. Culturing non-regenerative mouse cardiomyocytes or human heart tissue with these niche factors reactivated progenitor gene expression and cell cycle activity. In summary, this spatio-temporal cell type atlas provides valuable insights into the heterocellular interactions that control cardiac repair. HighlightsO_LIscRNA-seq and in situ sequencing reveal spatio-temporal dynamics of heart repair C_LIO_LILocal heterocellular communication niches coordinate overall wound response C_LIO_LIFibroblast cell cycle silencing by Trem2high macrophages suppresses excessive fibrosis C_LIO_LICardiomyocyte plasticity is promoted by myeloid and lymphoid cells C_LI

systems biology↗

bioRxiv2024

Lysosomal signalling pathways influence heart rhythm, and regulate atrial function

In the heart, endogenous nicotinic acid adenine dinucleotide phosphate (NAADP) triggers lysosomal calcium (Ca2+) release to augment sarcoplasmic reticulum (SR) Ca2+ sequestration, producing larger Ca2+ transients. However, the role of lysosomal Ca2+ signals in pacemaker activity, a distinct Ca2+-operated function of the sinoatrial node (SAN), or in the atrial myocardium has not been investigated. Pharmacological or genetic ablation of the NAADP pathway inhibits the spontaneous beating rate response to beta-adrenergic stimulation in intact SAN. We found intracellular signaling microdomains between lysosomes and neighboring SR or mitochondria in mouse, and goat tissue. The spatial relationship between lysosomes and other Ca2+-handling organelles are altered in goat atrial fibrillation. Furthermore, we demonstrate atrial myocytes produce cAMP in response to lysosomal signaling, adding a novel trigger for cyclic nucleotide signaling. Our findings support the hypothesis that lysosomal Ca2+ signaling contributes to regulation of cardiomyocyte cAMP levels and pacemaker activity.

physiology↗