Single-Cell Proteomics Uncovers Cell-Specific Proteins in Vascular Health and Marfan Syndrome Disease
Junedh M. Amrute, Lihua Jiang, Nikhita Bolar, Kelly Higa, Chenchen Zhu, Ruiqi Jian, Jennifer Kim, Matthew Duda, Anna Marie Puaala, Avani Klinder, Alex Dalal, Albert Pedroza, Dieter P. Reinhardt, Paul Cheng, Michael Snyder, Michael P. FischbeinBACKGROUND:
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.