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Mocci, G.

Publications and source records attributed to Mocci, G..

3 recordsLinked to original sources
bioRxiv2025

Spatial gene expression of human coronary arteries revealed the molecular features of diffuse intimal thickening in explanted hearts

BackgroundDiffuse intimal thickening (DIT) is a pre-clinical stage of atherosclerosis characterized by thickened intima. The molecular basis of its susceptibility to atherogenesis is unknown, and mechanistic investigations cannot be performed in commonly used mouse models, in which DIT does not exist. Vascular smooth muscle cells (SMCs) are the predominant cell type that occupies the intima and media of DIT. The molecular differences between these two layers may reveal the earliest phenotypic changes in SMCs to promote atherosclerosis. MethodsWe benchmarked the RNA quality of human coronary arteries from autopsies (n=7) and freshly explanted hearts (n=7) and performed Visium spatial gene expression on tissue sections with DIT. SMC-enriched intima and media were compared to find differentially expressed genes. The gene ontology features of SMC-enriched intima in this study were also compared to those in the atherosclerotic lesions, as previously revealed by single-cell RNA-sequencing studies. ResultsAlthough autopsy samples met the RNA quality standard for Visium (DV200 [≥] 30%), only arteries from freshly explanted hearts exhibited reliable performance. Genes enriched in TGF-{beta}-mediated remodeling of the extracellular matrix were overrepresented in the intima, including versican and biglycan. SMCs enriched in the intima are dedifferentiated, but unlike those in the lesions, they are not proinflammatory. ConclusionsOur findings indicate that autopsy samples are not ideal to distinguish subtle differences among cell phenotypes. Dedifferentiated SMCs in the DIT are distinct from the proinflammatory SMCs in atherosclerotic lesions. SMCs in thickened intima may lead to lipid retention but not necessarily the onset of atherosclerosis. Research Perspective1) What is New? O_LIPostmortem coronary arteries, which are frequently collected by biobanks, have degraded RNA, which are not suitable for identifying subtle differences in the transcriptome profiles. C_LIO_LICoronary arteries from explanted hearts allow for more faithful representation of spatial gene expression across the vessel wall as compared to ones from autopsy hearts. C_LIO_LIThickened intima in diffuse intimal thickening, which exists in everyone, is unlikely to undergo atherogenesis without additional stimuli such as inflammation. C_LI 2) What Question Should be Addressed Next? O_LIThe current RNA quality standard of spatial transcriptomics needs to be carefully benchmarked in biobank samples to control sequencing performance and meaningful data interpretation. C_LIO_LIHow inflammation changes smooth muscle cell phenotypes may explain why everyone has diffuse intimal thickening, but those with chronic inflammatory disease have a high risk of coronary artery disease. C_LIO_LIFuture research should focus on the interplay between smooth muscle cell phenotypes and the extracellular matrix to understand the etiology of coronary artery disease. C_LI

pathology↗
bioRxiv2025

A comprehensive molecular atlas of the cell types in the mouse liver

The liver plays a crucial role in essential physiological processes, and its impaired function due to liver fibrosis from various causes is an increasingly significant health issue. The livers functionality relies on the precise arrangement of its cellular structures, yet the molecular architecture of these units remains only partially understood. We created a comprehensive molecular atlas detailing all the major cell types present in the adult mouse liver through deep single-cell RNA sequencing. Our analysis offers new insights into hepatic endothelial and mesenchymal cells, specifically highlighting the differences between the cells of the periportal microvasculature, the sinusoids, and the portal vein, the latter exhibiting a mixed arterio-venous phenotype. We identified distinct subpopulations of hepatic stellate cells, fibroblasts, and vascular mural cells located in different anatomical regions. Comparisons with transcriptomic data from disease models indicate that a previously unrecognized capsular population of hepatic stellate cells expands in response to fibrotic disease. Our findings reveal that various fibroblast subpopulations respond differently to pathological insults. This data resource will be invaluable for advancing therapeutic interventions targeting hepatic diseases.

cell biology↗
bioRxiv2020

Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2 - implications for microvascular inflammation and hypercoagulopathy in COVID-19 patients

Accumulating clinical observations implicate vascular inflammation as an underlying cause of coagulopathy in severely ill COVID-19 patients and it was recently suggested that SARS-CoV-2 virus particles infect endothelial cells. Here, we show that endothelial cells do not express angiotensin-converting enzyme-2 (ACE2), the SARS-CoV-2 receptor. Instead, pericytes and microvascular smooth muscle cells express ACE2 in an organotypic manner. Pericyte deficiency leads to increased endothelial expression and release of Von Willebrand factor and intravascular platelet and fibrin aggregation, suggesting that pericytes limit endothelial pro-thrombotic responses. That pericytes and not endothelial cells express ACE2 may provide important clues to the pathology of COVID-19, as pericytes are normally shielded behind an endothelial barrier and may get infected only when this barrier is compromised by COVID-19 risk factors.

pathology↗