Bruker-MUSC Center of Excellence, Clinical Glycomics, Medical University of South Carolina, Charleston, SC, USA.
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA.
Expert Rev Proteomics. 2021 Jun;18(6):423-436. doi: 10.1080/14789450.2021.1941893. Epub 2021 Jul 24.
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.
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.
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.
成纤维细胞通过分泌细胞外基质来维持组织和器官的内稳态,细胞外基质会影响基质中附近细胞的信号转导。成纤维细胞信号转导的改变会导致许多疾病状态,而成纤维细胞分泌的细胞外基质已被用于根据患者的预后、复发和治疗耐药性对其进行分层。成像质谱技术的最新进展使人们能够在临床相关的组织样本中获取单细胞成纤维细胞及其细胞外基质龛。
我们回顾了在复杂的组织微环境中获取成纤维细胞表达的蛋白质组学的生物学和技术挑战,以及新的解决方案。综述内容涵盖了用于单细胞成纤维细胞分析的常规蛋白质组学方法,以及当前通过成像质谱方法获取单细胞成纤维细胞蛋白质组的方法。还提出了基于细胞信号转导的靶向和评估单细胞基质蛋白质组的策略。
从成纤维细胞及其细胞外基质龛中定义蛋白质组特征的前景在于发现新的疾病标志物,并能够改进治疗方法。有几种成像质谱方法可用于从临床获得的样本中定义病理变化条件下的成纤维细胞。需要不断的技术进步来获取和理解基质蛋白质组,并将测试应用于临床。