Deep Visual Proteomics links vascular smooth muscle cell phenotypes to atherosclerotic plaque stability
Kratz, E.; Sinha, A.; Adeshara, T.; Paloschi, V.; Sachs, N.; Pauli, J.; Glukha, N.; Huber, A.; Schanda, S.; Metousis, A.; Heymann, T.; Branzan, D.; Bleckwehl, T.; Hayat, S.; Maegdefessel, L.; Mann, M.
Show abstract
Vascular smooth muscle cells (VSMCs) drive atherosclerosis through phenotypic switching, yet their spatial organization and protein signatures within plaques remain poorly characterized. Here, we applied Deep Visual Proteomics (DVP) to dissect more than 500 VSMC neighborhoods across 24 human carotid plaques and profile VSMC plasticity in disease. To functionally interpret these tissue proteomes, we built a reference atlas of primary VSMCs driven toward five phenotypes by TGF-{beta}, PDGF-BB, osteogenic stimuli, IL-1{beta}, or cholesterol, quantifying over 10,000 proteins. We integrated tissue and reference proteomes with a deep-learning framework that assigns functional phenotypes to each neighborhood. This revealed spatially distinct phenotype distributions and a shift toward dedifferentiated states in unstable plaques. Knockdown of four candidates (TNC, TNFAIP2, AEBP1, PLK1) validated operational roles during phenotypic switching. Our approach functionally annotates spatial proteomes and links VSMC plasticity to plaque instability in carotid artery disease.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Early Endosome Capture Proteomics and its Application to Amyloid Precursor Protein Intramembrane Processing by β and γ-Secretases 96%
- Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth 96%
- ASPSCR1-TFE3 reprograms transcription by organizing enhancer loops around hexameric VCP/p97 95%
Similar papers in this journal
Similar papers in this journal
- Integrative, high-resolution analysis of single cell gene expression across experimental conditions with PARAFAC2-RISE 95%
- Conserved epigenetic regulatory logic infers genes governing cell identity 94%
- Emergence of synchronized multicellular mechanosensing from spatiotemporal integration of heterogeneous single-cell information transfer 94%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.