蛋白质组学
利基
计算生物学
医学
生物
神经科学
生态学
遗传学
基因
作者
Aleix Rius Rigau,Yi-Nan Li,Alexandru-Emil Matei,Andrea-Hermina Györfi,Peter‐Martin Bruch,Sarah Koziel,Veda Devakumar,Armando Gabrielli,Alexander Kreuter,Jiucun Wang,Sascha Dietrich,Georg Schett,Jörg H W Distler,Minrui Liang
标识
DOI:10.1161/circresaha.123.323299
摘要
BACKGROUND: Systemic sclerosis (SSc) is a connective tissue disease that can serve as a model to study vascular changes in response to inflammation, autoimmunity, and fibrotic remodeling. Although microvascular changes are the earliest histopathologic manifestation of SSc, the vascular pathophysiology remains poorly understood. OBJECTIVE: We applied spatial proteomic approaches to deconvolute the heterogeneity of vascular cells at the single-cell level in situ and characterize cellular alterations of the vascular niches of patients with SSc. METHODS AND RESULTS: Skin biopsies of patients with SSc and control individuals were analyzed by imaging mass cytometry, yielding a total of 90 755 cells including 2987 endothelial cells and 4096 immune cells. We identified 7 different subpopulations of blood vascular endothelial cells (VECs), 2 subpopulations of lymphatic endothelial cells, and 3 subpopulations of pericytes. A novel population of CD34 + ;αSMA + (α-smooth muscle actin);CD31 + VECs was more common in SSc, whereas endothelial precursor cells were decreased. Co-detection by indexing and tyramide signal amplification confirmed these findings. The microenvironment of CD34 + ;αSMA + ;CD31 + VECs was enriched for immune cells and myofibroblasts, and CD34 + ;αSMA + ;CD31 + VECs expressed markers of endothelial-to-mesenchymal transition. The density of CD34 + ;αSMA + ;CD31 + VECs was associated with clinical progression of fibrosis in SSc. CONCLUSIONS: Using spatial proteomics, we unraveled the heterogeneity of vascular cells in control individuals and patients with SSc. We identified CD34 + ;αSMA + ;CD31 + VECs as a novel endothelial cell population that is increased in patients with SSc, expresses markers for endothelial-to-mesenchymal transition, and is located in close proximity to immune cells and myofibroblasts. CD34 + ;αSMA + ;CD31 + VEC counts were associated with clinical outcomes of progressive fibrotic remodeling, thus providing a novel cellular correlate for the crosstalk of vasculopathy and fibrosis.
科研通智能强力驱动
Strongly Powered by AbleSci AI