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血管床体外培养内皮细胞的蛋白质组学全景。

The proteomic landscape of in vitro cultured endothelial cells across vascular beds.

机构信息

Department of Molecular Hematology, Sanquin Research, Amsterdam, The Netherlands.

出版信息

Commun Biol. 2024 Aug 14;7(1):989. doi: 10.1038/s42003-024-06649-w.

Abstract

Blood vessel endothelial cells (EC) display heterogeneity across vascular beds, which is anticipated to drive site-specific vascular pathology. This heterogeneity is assessed using transcriptomics in vivo, and functional assays in vitro, but how proteomes compare across human in vitro cultured ECs remains incompletely characterized. We generated an in-depth human EC proteomic landscape (>8000 proteins) across six organs and two in vitro models in steady-state and upon IFNγ-induced inflammation. EC proteomes displayed a high similarity and organ-specific proteins were limited. Variation between ECs was mainly based on proliferation and differentiation processes in which Blood outgrowth endothelial cells (BOEC) and Human umbilical vein cells (HUVEC) represented the extremes of proteomic phenotypes. The IFNγ response was highly conserved across all samples. Harnessing dynamics in protein abundances we delineated VWF and VE-Cadherin correlation networks. This EC landscape provides an extensive proteomic addition in studying EC biology and heterogeneity from an in vitro perspective.

摘要

血管内皮细胞(EC)在血管床中表现出异质性,预计这将导致特定部位的血管病理学。这种异质性可以通过体内转录组学和体外功能测定来评估,但人类体外培养的 EC 之间的蛋白质组如何比较仍不完全清楚。我们在稳态和 IFNγ 诱导的炎症下,在六个器官和两种体外模型中生成了深入的人类 EC 蛋白质组景观(>8000 种蛋白质)。EC 蛋白质组表现出高度相似性,器官特异性蛋白质有限。EC 之间的差异主要基于增殖和分化过程,其中血管外生内皮细胞(BOEC)和人脐静脉细胞(HUVEC)代表了蛋白质组表型的极端。IFNγ 反应在所有样本中高度保守。利用蛋白质丰度的动态变化,我们描绘了 VWF 和 VE-Cadherin 相关网络。该 EC 图谱从体外角度为研究 EC 生物学和异质性提供了广泛的蛋白质组学补充。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c344/11324761/ec3f5167cc72/42003_2024_6649_Fig1_HTML.jpg

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