ABSTRACT

Introduction

Fibroblasts maintain tissue and organ homeostasis through output of extracellular matrix that affects nearby cell signaling within the stroma. Altered fibroblast signaling contributes to many disease states and extracellular matrix secreted by fibroblasts has been used to stratify patient by outcome, recurrence, and therapeutic resistance. Recent advances in imaging mass spectrometry allow access to single cell fibroblasts and their ECM niche within clinically relevant tissue samples.

Areas covered

We review biological and technical challenges as well as new solutions to proteomic access of fibroblast expression within the complex tissue microenvironment. Review topics cover conventional proteomic methods for single fibroblast analysis and current approaches to accessing single fibroblast proteomes by imaging mass spectrometry approaches. Strategies to target and evaluate the single cell stroma proteome on the basis of cell signaling are presented.

Expert opinion

The promise of defining proteomic signatures from fibroblasts and their extracellular matrix niches is the discovery of new disease markers and the ability to refine therapeutic treatments. Several imaging mass spectrometry approaches exist to define the fibroblast in the setting of pathological changes from clinically acquired samples. Continued technology advances are needed to access and understand the stromal proteome and apply testing to the clinic.

中文翻译：

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成纤维细胞的质谱成像：承诺与挑战

摘要

介绍

成纤维细胞通过输出影响基质内附近细胞信号传导的细胞外基质来维持组织和器官的稳态。改变的成纤维细胞信号转导导致许多疾病状态，并且由成纤维细胞分泌的细胞外基质已被用于根据结果、复发和治疗抗性对患者进行分层。成像质谱法的最新进展允许在临床相关组织样本中访问单细胞成纤维细胞及其 ECM 生态位。

涵盖的领域

我们回顾了复杂组织微环境中成纤维细胞表达的蛋白质组学访问的生物学和技术挑战以及新的解决方案。审查主题涵盖用于单成纤维细胞分析的常规蛋白质组学方法以及通过成像质谱法获取单成纤维细胞蛋白质组的当前方法。提出了基于细胞信号的靶向和评估单细胞基质蛋白质组的策略。

专家意见

定义成纤维细胞及其细胞外基质生态位的蛋白质组学特征的前景是发现新的疾病标志物和改进治疗方法的能力。存在几种成像质谱方法来定义成纤维细胞在临床采集样本的病理变化环境中。需要持续的技术进步来获取和了解基质蛋白质组并将测试应用于临床。