Kaiser Matthias, Jug Florian, Julou Thomas, Deshpande Siddharth, Pfohl Thomas, Silander Olin K, Myers Gene, van Nimwegen Erik
Biozentrum, University of Basel and Swiss Institute of Bioinformatics, Klingelbergstrasse 50/70, 4056, Basel, Switzerland.
Max Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstraße 108, 01307, Dresden, Germany.
Nat Commun. 2018 Jan 15;9(1):212. doi: 10.1038/s41467-017-02505-0.
Much is still not understood about how gene regulatory interactions control cell fate decisions in single cells, in part due to the difficulty of directly observing gene regulatory processes in vivo. We introduce here a novel integrated setup consisting of a microfluidic chip and accompanying analysis software that enable long-term quantitative tracking of growth and gene expression in single cells. The dual-input Mother Machine (DIMM) chip enables controlled and continuous variation of external conditions, allowing direct observation of gene regulatory responses to changing conditions in single cells. The Mother Machine Analyzer (MoMA) software achieves unprecedented accuracy in segmenting and tracking cells, and streamlines high-throughput curation with a novel leveraged editing procedure. We demonstrate the power of the method by uncovering several novel features of an iconic gene regulatory program: the induction of Escherichia coli's lac operon in response to a switch from glucose to lactose.
关于基因调控相互作用如何在单细胞中控制细胞命运决定，仍有许多未知之处，部分原因是难以在体内直接观察基因调控过程。我们在此介绍一种新颖的集成装置，它由一个微流控芯片和配套的分析软件组成，能够对单细胞的生长和基因表达进行长期定量跟踪。双输入母机（DIMM）芯片能够对外界条件进行可控的连续变化，从而直接观察单细胞对变化条件的基因调控反应。母机分析仪（MoMA）软件在细胞分割和跟踪方面达到了前所未有的精度，并通过一种新颖的杠杆编辑程序简化了高通量管理。我们通过揭示一个标志性基因调控程序的几个新特征来展示该方法的强大之处：大肠杆菌乳糖操纵子在从葡萄糖转换到乳糖时的诱导。
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