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Glycoproteomics of the Extracellular Matrix: A Method for Intact Glycopeptide Analysis Using Mass Spectrometry
Published on: April 21, 2017
Single-Cell Proteomics Uncovers Cell-Specific Proteins in Vascular Health and Marfan Syndrome Disease-Brief Report
Junedh M Amrute1, Lihua Jiang2, Nikhita Bolar3
1Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, Washington University School of Medicine, St. Louis, MO (J.M.A.).
Background:
The vascular system is the largest organ in the body and underlies most chronic diseases, yet the molecular mechanisms that govern its plasticity remain poorly defined.
Methods:
We applied single-cell proteomics in vascular disease, integrating it with single-cell transcriptomics to map protein regulation in healthy and Marfan syndrome aortas.
Results:
This approach uncovered cell type-specific and cell state-specific proteins missed at the transcriptional level. Notably, we identified a decoupling of fibrillin-1 RNA and protein abundance, suggesting altered protein regulation as a potential contributor to aortic degeneration. Single-cell proteomics further resolved modulated smooth muscle cell states enriched for matrix effectors (AEBP1 [adipocyte enhancer binding protein 1], HTRA1 [high-temperature requirement A serine peptidase 1], FN1 [fibronectin 1]) and uniquely protein-level regulators (GLIPR2 [GLI pathogenesis-related 2], ITGB2 [integrin beta-2], and CD151 [cluster of differentiation 151 antigen]).
Conclusions:
Together, these findings establish the human single-cell proteomic atlas of the aorta, reveal altered FBN1 (fibrillin-1) protein regulation in both human and mouse Marfan syndrome, and position single-cell proteomics as a transformative framework for decoding vascular plasticity and identifying actionable effectors in disease.
