Biology subjects

Murareanu, B. M.

Publications and source records attributed to Murareanu, B. M..

4 recordsLinked to original sources

bioRxiv2025

Human pluripotent stem cell-derived atrioventricular node-like pacemaker cells exhibit biological conduction bridge properties in vitro and in vivo

The atrioventricular node (AVN) ensures synchronized heart contractions by establishing the electrical connection between the atria and ventricles. Dysfunction of the pacemaker cells of the AVN leads to atrioventricular block (AV block), a life-threatening condition managed with electronic pacemakers (EPMs). EPMs have drawbacks that could be overcome by a human pluripotent stem cell (hPSC)-derived biological conduction bridge (BioCB). Recent studies demonstrated the differentiation of AVN-like cells from hPSCs, but their conduction properties upon engraftment in vivo remain unexplored. Here we report the generation of AVN-like pacemaker cells (AVNLPCs) from hPSCs using WNT and BMP signaling modulation. These AVNLPCs transcriptionally resemble fetal AVN pacemaker cells, exhibit pacemaker action potentials, and display unique AVN-like conduction properties. Notably, when transplanted into the guinea pig heart, AVNLPCs replicate the functional properties of the AVN. Our study highlights the potential of an AVNLPC-based BioCB as novel cell therapy to improve treatment for AV block patients.

developmental biology↗

bioRxiv2024

Single-cell transcriptome analysis reveals CD34 as a novel marker of human sinoatrial node pacemaker cardiomyocytes

The sinoatrial node (SAN) regulates the heart rate throughout life. Failure of this primary pacemaker results in life-threatening, slow heart rhythm. Despite its important function, the cellular and molecular composition of the human SAN is not completely resolved. Particularly, no cell surface marker to identify and isolate SAN pacemaker cells has been reported to date. Here we used single-nuclei/cell RNA sequencing of fetal and human pluripotent stem cell (hPSC)- derived SAN cells and show that the SAN consists of three subtypes of pacemaker cells, including Core SAN, SAN, and Transitional Cells. Our study identified a host of novel Core SAN markers including MYH11, BMP4, and the cell surface antigen CD34. We demonstrate that sorting for CD34+ cells from cardiac hPSC differentiations enriches for SAN cells with a functional pacemaker phenotype. This novel SAN pacemaker cell surface marker is highly valuable for future hPSC- based disease modelling, drug discovery, cell replacement therapies, as well as the delivery of therapeutics to SAN cells in vivo using antibody-drug conjugates.

cell biology↗

bioRxiv2021

High-throughput small molecule screen identifies inhibitors of microsporidia invasion and proliferation in C. elegans.

Microsporidia are a diverse group of fungal-related obligate intracellular parasites that infect most animal phyla. Despite the emerging threat that microsporidia have become to humans and agricultural animals, few reliable treatment options exist. To identify novel chemical inhibitors of microsporidia infection, we developed a high-throughput screening method using Caenorhabditis elegans and the microsporidia species Nematocida parisii. We screened the Spectrum Collection of 2,560 FDA-approved compounds and natural products to identify compounds that prevent C. elegans progeny inhibition caused by N. parisii infection. We developed a semi-automated method for quantifying C. elegans progeny number in liquid culture, confirming 11 candidate microsporidia inhibitors. We show that five compounds prevent microsporidia infection by inhibiting spore firing, and demonstrate that one compound, dexrazoxane, slows infection progression. We also show that these compounds have activity against several other microsporidia species, including those which infect humans. Together, our results demonstrate the effectiveness of C. elegans as a model host for drug discovery against intracellular pathogens and provide a scalable high-throughput system for the identification and characterization of additional microsporidia inhibitors.

microbiology↗

bioRxiv2021

Comprehensive survey of microsporidia reveals extensive ecological and phenotypic diversity

Microsporidia are a large group of fungal-related obligate intracellular parasites. Though many microsporidia species have been identified over the past 160 years, there is a lacking depiction of the full diversity of this phylum. To systematically describe the characteristics of these parasites, we created a database of 1,440 species and their attributes, including the hosts they infect and spore characteristics. We find that microsporidia have been reported to infect 16 metazoan and four protozoan phyla, with smaller phyla being underrepresented. Most species are only reported to infect a single host, but those that are generalists are also more likely to infect a broader set of host tissues. Strikingly, polar tubes are 3-fold longer in species that infect tissues besides the intestine, suggesting that polar tube length is a determinant of tissue specificity. Phylogenetic analysis revealed four clades which each contain microsporidia infecting hosts from all major habitats. Although related species are more likely to infect similar hosts, we observe examples of changes in host specificity and convergent evolution. Taken together, our results show that microsporidia display vast diversity in their morphology and the hosts they infect, illustrating the flexibility of these parasites to evolve new traits.

microbiology↗