Gaudet Suzanne, Miller-Jensen Kathryn
Department of Cancer Biology and Center for Cancer Systems Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA; Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Trends Biotechnol. 2016 Jun;34(6):458-469. doi: 10.1016/j.tibtech.2016.02.009. Epub 2016 Mar 9.
Genetically identical cells respond heterogeneously to uniform environmental stimuli. Consequently, investigating the signaling networks that control these cell responses using 'average' bulk cell measurements can obscure underlying mechanisms and misses information emerging from cell-to-cell variability. Here we review recent technological advances including live-cell fluorescence imaging-based approaches and microfluidic devices that enable measurements of signaling networks, dynamics, and responses in single cells. We discuss how these single-cell tools have uncovered novel mechanistic insights for canonical signaling pathways that control cell proliferation (ERK), DNA-damage responses (p53), and innate immune and stress responses (NF-κB). Future improvements in throughput and multiplexing, analytical pipelines, and in vivo applicability will all significantly expand the biological information gained from single-cell measurements of signaling pathways.
基因相同的细胞对均匀的环境刺激会产生异质性反应。因此，使用“平均”的大量细胞测量来研究控制这些细胞反应的信号网络，可能会掩盖潜在机制，并遗漏细胞间变异性所产生的信息。在这里，我们回顾了最近的技术进展，包括基于活细胞荧光成像的方法和微流控装置，这些技术能够测量单细胞中的信号网络、动力学和反应。我们讨论了这些单细胞工具如何为控制细胞增殖（ERK）、DNA损伤反应（p53）以及先天免疫和应激反应（NF-κB）的经典信号通路揭示了新的机制见解。通量和多重分析、分析流程以及体内适用性方面未来的改进，都将显著扩展从信号通路的单细胞测量中获得的生物学信息。
