Single cell transcriptome analysis: a chemical approach for studying mammalian gene regulation

有了这个奖项，生命过程的化学计划正在支持南加州大学钟教授的研究。 钟教授将通过单细胞转录组分析研究哺乳动物细胞的重编程机制。虽然传统的细胞裂解物方法提供了大量的RNA用于分析，但时间和定量基因表达信息被擦除并在裂解物中的所有细胞中平均。基因调控关系的“丢失的钥匙”将在单细胞转录组学分析中找到，而不是目前在许多传统研究中使用的平均细胞裂解物技术。 Zhong团队将诱导细胞中重编程因子（RFs）的表达，以确定哪些基因在单细胞水平上受到诱导的RFs的调控。这项研究将提供分子信息来剖析重编程的遗传机制，加深我们对细胞命运决定的理解，并展示一种新的化学方法，单细胞转录组分析，用于化学/细胞生物学。单细胞转录组分析的微流体/细胞分选/qPCR方法预计将对化学/生物学界面的问题具有广泛的科学应用，远远超出了该资助的范围。 同样重要的是，该项目将促进高中、本科和研究生各级的教育和培训，并努力扩大代表性不足的少数群体对现代化学生物学研究的参与。 社区推广和“虚拟实验室”开发计划也已到位，预计将扩大这种多学科方法在化学，纳米工程和细胞生物学交叉领域的研究范围。

With this award, the Chemistry of Life Processes program is supporting the research of Professor Zhong of the University of Southern California. Professor Zhong will investigate the reprogramming mechanism of mammalian cells with single-cell transcriptome analysis. Although traditional cell lysate approaches provide significant quantities of RNA for analysis, the temporal and quantitative gene expression information is erased and averaged among all cells in the lysate. The "lost key" of gene regulatory relationships is to be found in single-cell transcriptomic analysis as opposed to the averaged cell lysate-techniques currently used in many traditional studies. The Zhong group will induce the expression of reprogramming factors (RFs) in cells to determine which genes are regulated by the induced-RFs at the single-cell level. This study will provide molecular information to dissect the genetic mechanism of reprogramming, deepen our understanding of cell fate decision, and demonstrate a novel chemical approach, single-cell transcriptome analysis, for chemical/cell biology. The microfluidics/cell sorting/qPCR approach to single cell transcriptome analysis is expected to have broad scientific applications to problems at the chemistry/biology interface, far beyond the scope of this grant. As important, the project will contribute to education and training at the high school, undergraduate and graduate levels and involve efforts to broaden participation of under-represented minorities in modern chemical biology research. Plans for community outreach and "virtual lab" development also in place, and expected to widen the reach of this multi-disciplinary approach to research at the intersection of at the chemistry, nanoscale engineering and cell biology.