Chimpanzee fibroblasts exhibit greater adherence and migratory phenotypes than human fibroblasts
Chimpanzee fibroblasts exhibit greater adherence and migratory phenotypes than human fibroblasts
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DOI：
10.1101/838755
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发表时间：
2019-11
期刊：
影响因子：
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通讯作者：
Trisha M. Zintel;D. Ducey;C. Babbitt
中科院分区：
文献类型：
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作者：
Trisha M. Zintel;D. Ducey;C. Babbitt
背景与目的：以往的研究发现，人类和黑猩猩之间存在细胞粘附途径的基因表达差异。在这里，我们使用比较细胞生物学方法来分析细胞粘附表型的种间差异，以便更好地了解物种上皮细胞之间的基本生物学差异，这些差异可能是我们在伤口愈合和癌症中看到的生物体水平差异的基础。方法我们使用人类和黑猩猩的皮肤成纤维细胞系来测定细胞粘附和迁移。然后，我们利用来自暴露于癌症/伤口愈合模拟物的相同细胞系的已发表的RNA-Seq数据来确定哪些基因表达变化可能对应于物种之间细胞粘附动力学的改变。结果黑猩猩成纤维细胞的粘附和迁移能力明显强于人成纤维细胞，黑猩猩成纤维细胞的粘附速度快，粘附时间长，进入“伤口”的速度快。基因表达数据表明，增强的黑猩猩成纤维细胞的粘附特性可能是由于黑猩猩成纤维细胞表现出显着更高的表达细胞和粘着斑分子基因比人类细胞，无论是在伤口愈合试验和休息。结论和影响黑猩猩成纤维细胞表现出更强的粘附和更大的细胞迁移比人成纤维细胞。这可能是由于粘着斑和细胞粘附分子（如整合素、层粘连蛋白和钙粘蛋白）以及ECM蛋白（如胶原蛋白）的不同基因表达所致。这是为数不多的几项研究之一，表明这些基因表达的差异在密切相关的物种之间可以体现在细胞生物学的根本差异。我们的研究结果为物种特异性细胞生物学表型以及它们如何影响更复杂的性状（如癌症转移和伤口愈合）提供了更好的见解。
Background and objectives Previous work has identified that gene expression differences in cell adhesion pathways exist between humans and chimpanzees. Here, we used a comparative cell biology approach to assay interspecies differences in cell adhesion phenotypes in order to better understand the basic biological differences between species’ epithelial cells that may underly the organism-level differences we see in wound healing and cancer. Methodology We used skin fibroblast cell lines from humans and chimpanzees to assay cell adhesion and migration. We then utilized published RNA-Seq data from the same cell lines exposed to a cancer / wound-healing mimic to determine what gene expression changes may be corresponding to altered cellular adhesion dynamics between species. Results The functional adhesion and migration assays revealed that chimpanzee fibroblasts adhered sooner and remained adherent for significantly longer and move into a “wound” at faster rate than human fibroblasts. The gene expression data suggest that the enhanced adhesive properties of chimpanzee fibroblasts may be due to chimpanzee fibroblasts exhibiting significantly higher expression of cell and focal adhesion molecule genes than human cells, both during a wound healing assay and at rest. Conclusions and implications Chimpanzee fibroblasts exhibit stronger adhesion and greater cell migration than human fibroblasts. This may be due to divergent gene expression of focal adhesion and cell adhesion molecules, such as integrins, laminins, and cadherins, as well as ECM proteins like collagens. This is one of few studies demonstrating that these divergences in gene expression between closely related species can manifest in fundamental differences in cell biology. Our results provide better insight into species-specific cell biology phenotypes and how they may influence more complex traits, such as cancer metastasis and wound healing.