Abstract

Expanding the Scope of Systems Biology Using Single Cells

David Ruff, Visiting Senior Research Fellow, Oxford University, UK, Principal Scientist , Fluidigm Corporation

Systems biology aims to decipher the molecular interactions that underlie biological responses by collecting a multitude of measurements on cellular attributes. Examination of the genomic landscape coupled to RNA expression signatures facilitates a high power of analysis for illuminating frameworks of modular circuitry and gene regulatory networks. A shortcoming of many systems biology study designs has been reliance on data from large numbers of pooled cells, with the resultant global population averaging of interrogated parameters. Individual and distinct cells within large populations often instigate significant biological cascades; however, their contributions to measurements are masked. Accessing system-level datasets on such important subpopulations requires single-cell analytical approaches. Recent advances in integrated fluidic circuitry have enabled the development of specialized technology for single-cell analysis: the Fluidigm® C1TM system. The C1 readily integrates single-cell isolation and generation of templates for both qPCR and next-generation sequencing analysis. We illustrate systems biology profiling for fundamental biomarkers using cancer and stem cell lines. These results highlight the individuality of cellular states in seemingly homogeneous cell populations. Taken with newly emerging applications and workflows, the C1 has become a powerful addition in the array of technologies to further systems biology investigations.