Center for Data Sciences, Brigham and Women's Hospital.
Division of Genetics, Brigham and Women's Hospital and Harvard Medical School, Boston.
Curr Opin Rheumatol. 2018 Jan;30(1):65-71. doi: 10.1097/BOR.0000000000000455.
Stroma is a broad term referring to the connective tissue matrix in which other cells reside. It is composed of diverse cell types with functions such as extracellular matrix maintenance, blood and lymph vessel development, and effector cell recruitment. The tissue microenvironment is determined by the molecular characteristics and relative abundances of different stromal cells such as fibroblasts, endothelial cells, pericytes, and mesenchymal precursor cells. Stromal cell heterogeneity is explained by embryonic developmental lineage, stages of differentiation to other cell types, and activation states. Interaction between immune and stromal cell types is critical to wound healing, cancer, and a wide range of inflammatory diseases. Here, we review recent studies of inflammatory diseases that use functional genomics and single-cell technologies to identify and characterize stromal cell types associated with pathogenesis.
High dimensional strategies using mRNA sequencing, mass cytometry, and fluorescence activated cell-sorting with fresh primary tissue samples are producing detailed views of what is happening in diseased tissue in rheumatoid arthritis, inflammatory bowel disease, and cancer. Fibroblasts positive for CD90 (Thy-1) are enriched in the synovium of rheumatoid arthritis patients. Single-cell RNA-seq studies will lead to more discoveries about the stroma in the near future.
Stromal cells form the microenvironment of inflamed and diseased tissues. Functional genomics is producing an increasingly detailed view of subsets of stromal cells with pathogenic functions in rheumatic diseases and cancer. Future genomics studies will discover disease mechanisms by perturbing molecular pathways with chemokines and therapies known to affect patient outcomes. Functional genomics studies with large sample sizes of patient tissues will identify patient subsets with different disease phenotypes or treatment responses.
基质是一个广义术语，指的是其他细胞所驻留的结缔组织基质。它由多种具有不同功能的细胞类型组成，如细胞外基质的维持、血管和淋巴管的发育以及效应细胞的募集。组织微环境由不同基质细胞（如成纤维细胞、内皮细胞、周细胞和间充质前体细胞）的分子特征和相对丰度决定。基质细胞的异质性可以通过胚胎发育谱系、向其他细胞类型分化的阶段和激活状态来解释。免疫细胞和基质细胞类型之间的相互作用对伤口愈合、癌症和广泛的炎症性疾病至关重要。在这里，我们综述了最近使用功能基因组学和单细胞技术来识别和描述与发病机制相关的基质细胞类型的炎症性疾病研究。
使用 mRNA 测序、质谱细胞术和荧光激活细胞分选与新鲜原发性组织样本的高维策略正在对类风湿关节炎、炎症性肠病和癌症中患病组织中发生的情况产生详细的认识。在类风湿关节炎患者的滑膜中，CD90（Thy-1）阳性的成纤维细胞增多。单细胞 RNA-seq 研究将在不久的将来导致对基质的更多发现。
基质细胞构成了炎症和患病组织的微环境。功能基因组学正在产生越来越详细的认识，了解风湿性疾病和癌症中具有致病功能的基质细胞亚群。未来的基因组学研究将通过用已知影响患者预后的趋化因子和治疗方法来干扰分子途径，从而发现疾病机制。对具有不同疾病表型或治疗反应的患者亚群进行具有大样本量的患者组织的功能基因组学研究将有助于识别。
