Phenomics Demonstrates Cytokines Additive Induction of Epithelial to Mesenchymal Transition.

IF 4.5 2区 生物学 Q2 CELL BIOLOGY
Alphonse Boché, Alexandra Landras, Mathieu Morel, Sabrina Kellouche, Franck Carreiras, Ambroise Lambert
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引用次数: 0

Abstract

Epithelial to mesenchymal transition (EMT) is highly plastic with a programme where cells lose adhesion and become more motile. EMT heterogeneity is one of the factors for disease progression and chemoresistance in cancer. Omics characterisations are costly and challenging to use. We developed single cell phenomics with easy to use wide-field fluorescence microscopy. We analyse over 70,000 cells and combined 53 features. Our simplistic pipeline allows efficient tracking of EMT plasticity, with a single statistical metric. We discriminate four high EMT plasticity cancer cell lines along the EMT spectrum. We test two cytokines, inducing EMT in all cell lines, alone or in combination. The single cell EMT metrics demonstrate the additive effect of cytokines combination on EMT independently of cell line EMT spectrum. The effects of cytokines are also observed at the front of migration during wound healing assay. Single cell phenomics is uniquely suited to characterise the cellular heterogeneity in response to complex microenvironment and show potential for drug testing assays.

表型组学证明细胞因子可诱导上皮细胞向间质转化
上皮细胞向间充质细胞的转化(EMT)具有高度可塑性,在这一过程中,细胞会失去粘附性,变得更加活跃。EMT 异质性是癌症疾病进展和化疗耐药性的因素之一。Omics 表征技术成本高昂,使用起来具有挑战性。我们利用易于使用的宽场荧光显微镜开发了单细胞表型组学。我们分析了 70,000 多个细胞,综合了 53 个特征。我们的简易管道可通过单一统计指标有效追踪 EMT 可塑性。我们沿着 EMT 谱区分了四种高 EMT 可塑性癌细胞系。我们测试了两种细胞因子,它们在所有细胞系中单独或联合诱导 EMT。单细胞 EMT 指标表明,细胞因子组合对 EMT 的叠加效应与细胞系 EMT 谱无关。在伤口愈合试验中,细胞因子的作用还体现在迁移的前端。单细胞表型组学非常适合描述细胞对复杂微环境反应的异质性,并显示出药物测试测定的潜力。
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来源期刊
CiteScore
14.70
自引率
0.00%
发文量
256
审稿时长
1 months
期刊介绍: The Journal of Cellular Physiology publishes reports of high biological significance in areas of eukaryotic cell biology and physiology, focusing on those articles that adopt a molecular mechanistic approach to investigate cell structure and function. There is appreciation for the application of cellular, biochemical, molecular and in vivo genetic approaches, as well as the power of genomics, proteomics, bioinformatics and systems biology. In particular, the Journal encourages submission of high-interest papers investigating the genetic and epigenetic regulation of proliferation and phenotype as well as cell fate and lineage commitment by growth factors, cytokines and their cognate receptors and signal transduction pathways that influence the expression, integration and activities of these physiological mediators. Similarly, the Journal encourages submission of manuscripts exploring the regulation of growth and differentiation by cell adhesion molecules in addition to the interplay between these processes and those induced by growth factors and cytokines. Studies on the genes and processes that regulate cell cycle progression and phase transition in eukaryotic cells, and the mechanisms that determine whether cells enter quiescence, proliferate or undergo apoptosis are also welcomed. Submission of papers that address contributions of the extracellular matrix to cellular phenotypes and physiological control as well as regulatory mechanisms governing fertilization, embryogenesis, gametogenesis, cell fate, lineage commitment, differentiation, development and dynamic parameters of cell motility are encouraged. Finally, the investigation of stem cells and changes that differentiate cancer cells from normal cells including studies on the properties and functions of oncogenes and tumor suppressor genes will remain as one of the major interests of the Journal.
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