Tissue specific human fibroblast differential expression based on RNAsequencing analysis
Tissue specific human fibroblast differential expression based on RNAsequencing analysis
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DOI：
10.1186/s12864-019-5682-5
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发表时间：
2019-04-23
期刊：
影响因子：
4.4
通讯作者：
Thibeault, Susan L.
中科院分区：
文献类型：
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作者：
Foote, Alexander G.;Wang, Ziyue;Thibeault, Susan L.
背景物理力，如机械应力，是组织内稳态所必需的，并影响细胞的基因表达。特别是，成纤维细胞已经表现出对细胞外基质的敏感性，并假定对各种机械负荷具有适应性。本研究的目的是比较声带成纤维细胞基因与不同解剖部位的细胞基因表达谱的差异，声带成纤维细胞因其独特的机械应激组织环境而闻名。结果利用RNA-seq技术，我们从7个来自健康身体的正常人类成纤维细胞原代细胞系中鉴定出差异表达基因程序(DEseq2)，这些细胞系包括：声带、气管、肺、腹部、头皮、上牙龈和软腭部。非监督基因表达分析得出了6216个基因在所有解剖部位的差异表达。等级聚类分析显示基于解剖部位来源的分组，而不是基于供者的分组，表明全球成纤维细胞表型的异质性。与性别和年龄相关的影响可以忽略不计。基于单组后两组比较的功能丰富分析显示，声带成纤维细胞内有几个与转录因子相关的功能主题，这些转录因子调节干细胞的多能性和细胞外基质成分，如细胞信号、迁移、增殖和分化潜能。结论人成纤维细胞存在整体形态分化现象，这一现象通过体外分析保持在孤立状态。表观遗传对声带组织的力学影响可能在动态平衡过程中独特地模拟和维持局部环境细胞生态位，声带成纤维细胞与其在胚胎发生期间建立的解剖、位置和发育起源明显专门化有关。
BackgroundPhysical 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.ResultsBy 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.ConclusionsHuman 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.