Department of Surgery, Division of Otolaryngology - Head and Neck Surgery, University of Wisconsin, Madison, WI, USA.
Department of Statistics, University of Wisconsin - Madison, College of Letters and Science, Madison, WI, USA.
BMC Genomics. 2019 Apr 23;20(1):308. doi: 10.1186/s12864-019-5682-5.
Physical forces, such as mechanical stress, are essential for tissue homeostasis and influence gene expression of cells. In particular, the fibroblast has demonstrated sensitivity to extracellular matrices with assumed adaptation upon various mechanical loads. The purpose of this study was to compare the vocal fold fibroblast genotype, known for its unique mechanically stressful tissue environment, with cellular counterparts at various other anatomic locales to identify differences in functional gene expression profiles.
By using RNA-seq technology, we identified differentially expressed gene programs (DEseq2) among seven normal human fibroblast primary cell lines from healthy cadavers, which included: vocal fold, trachea, lung, abdomen, scalp, upper gingiva, and soft palate. Unsupervised gene expression analysis yielded 6216 genes differentially expressed across all anatomic sites. Hierarchical cluster analysis revealed grouping based on anatomic site origin rather than donor, suggesting global fibroblast phenotype heterogeneity. Sex and age-related effects were negligible. Functional enrichment analyses based on separate post-hoc 2-group comparisons revealed several functional themes within the vocal fold fibroblast related to transcription factors for signaling pathways regulating pluripotency of stem cells and extracellular matrix components such as cell signaling, migration, proliferation, and differentiation potential.
Human fibroblasts display a phenomenon of global topographic differentiation, which is maintained in isolation via in vitro assays. Epigenetic mechanical influences on vocal fold tissue may play a role in uniquely modelling and maintaining the local environmental cellular niche during homeostasis with vocal fold fibroblasts distinctly specialized related to their anatomic positional and developmental origins established during embryogenesis.
物理力，如机械应力，对组织稳态至关重要，并影响细胞的基因表达。特别是成纤维细胞对细胞外基质表现出敏感性，认为在各种机械负荷下会发生适应性改变。本研究的目的是比较已知处于独特机械应激组织环境中的声带成纤维细胞基因型与其他不同解剖部位的细胞对应物，以确定功能基因表达谱的差异。
通过使用 RNA-seq 技术，我们在 7 个人类正常声带成纤维细胞原代细胞系中鉴定出差异表达的基因程序（DEseq2），这些细胞系来自健康尸体，包括：声带、气管、肺、腹部、头皮、上牙龈和软腭。非监督基因表达分析得出在所有解剖部位都有 6216 个差异表达的基因。层次聚类分析根据解剖部位起源而不是供体进行分组，表明全球成纤维细胞表型存在异质性。性别和年龄相关的影响可以忽略不计。基于单独的事后 2 组比较的功能富集分析揭示了与调节干细胞多能性和细胞外基质成分（如细胞信号转导、迁移、增殖和分化潜能）信号通路的转录因子相关的几个声带成纤维细胞的功能主题。
人类成纤维细胞表现出一种全局地形分化的现象，这种现象通过体外实验得以维持。声带组织的表观遗传机械影响可能在维持声带成纤维细胞的局部环境细胞生态位方面发挥作用，这些细胞明显专门化与其在胚胎发生过程中建立的解剖位置和发育起源有关。
