Basso, C. | Search bioRxiv

bioRxiv2026

Spatial proteomic profiling of cardiac stromal populations and microenvironments in systemic sclerosis-associated primary myocardial involvement

Objectives: To define cardiac stromal heterogeneity and spatial stromal-immune organization in systemic sclerosis-associated virus-negative myocarditis (SSc-VNM), a manifestation of primary SSc heart involvement. Methods: Imaging mass cytometry, a single-cell multiplexed spatial proteomic technology, was applied to endomyocardial biopsies from ten patients with SSc-VNM, seven with VNM associated with other systemic autoimmune rheumatic diseases (a-VNM) and nine with isolated VNM (i-VNM). Single-cell phenotyping, cellular-neighborhood and spatial-interaction analyses, and correlations with histological fibrosis were performed at patient level. Results: Among 82,673 segmented cells, we identified seven fibroblast phenotypes and one CD34+ stromal-cell population. The overall fibroblast/stromal compartment was expanded in SSc-VNM compared with i-VNM (adjusted p = 0.00973). The composition of fibroblasts/stromal cells differed profoundly in SSc-VNM compared with a-VNM and i-VNM, with numerical increases in CD34+ stromal cells and SOX9+ and PI16high/POSTNhigh fibroblasts and de-enrichment of FAPhigh/POSTNhigh fibroblasts and myofibroblasts. Spatial analysis identified ten cellular neighborhoods and revealed distinct SSc-VNM-associated patterns, including altered stromal-immune interaction networks. These included enriched interactions of CD34+ stromal cells and PI16high/POSTNhigh fibroblasts with CD163high/HLA-DR+ macrophages and CD68+ mast cells. PI16high/POSTNhigh and PI16-/POSTNhigh fibroblasts demonstrated the highest collagen type 1 expression among all stromal cell subsets across all VNM entities and PI16high/POSTNhigh fibroblasts were numerically increased in biopsies with [≥]10% fibrotic remodeling and were spatially associated with collagen-rich areas. Conclusions: Our findings refine current concepts of human fibrotic myocardial remodeling and support therapeutic targeting of specific stromal players such as POSTNhigh fibroblast subpopulations. Keywords: Systemic Sclerosis; Myocarditis; Myocardial Fibrosis; Fibroblasts; Imaging Mass Cytometry.

bioinformatics↗

bioRxiv2022

COVID-19 Neuropathology: evidence for SARS-CoV-2 invasion of Human Brainstem Nuclei

Neurological manifestations are common in COVID-19, the disease caused by SARS-CoV-2. Despite reports of SARS-CoV-2 detection in the brain and cerebrospinal fluid of COVID-19 patients, its still unclear whether the virus can infect the central nervous system, and which neuropathological alterations can be ascribed to viral tropism, rather than immune-mediated mechanisms. Here, we assess neuropathological alterations in 24 COVID-19 patients and 18 matched controls who died due to pneumonia / respiratory failure. Aside from a wide spectrum of neuropathological alterations, SARS-CoV-2-immunoreactive neurons were detected in specific brainstem nuclei of 5 COVID-19 subjects. Viral RNA was also detected by real-time RT-PCR. Quantification of reactive microglia revealed an anatomically segregated pattern of inflammation within affected brainstem regions, and was higher when compared to controls. While the results of this study support the neuroinvasive potential of SARS-CoV-2, the role of SARS-CoV-2 neurotropism in COVID-19 and its long-term sequelae require further investigation.

neuroscience↗