The analysis of individual cells is now a reality. Single-cell signatures may tell us a lot about the tissue microenvironment, differentiation, aging, or regeneration. For instance, tumor microenvironment contains multiple cell types including immune cells, stroma, cells of blood vessels, and all their chemical signals.
Communication of tumor cells with their microenvironment helps drive tumor progression. Single-cell analysis can explain this communication in great detail, potentially yielding new therapeutic approaches for targeting these signals.
Until recently, the sensitivity of most of the “omics” techniques (genomics, proteomics) was not sufficient enough to trace the contribution of individual components. Many current molecular biology techniques require multiple cells. This inevitably blends cell populations and, therefore, reports the average values.
“This is rapidly changing,” comments Daojing Wang, Ph.D., life sciences division, Lawrence Berkeley National Laboratory. “Single-cell analysis is a new frontier in omics. It will enable systems biology at the level of individual cells.” Single-cell technologies will help to understand the molecular stasis of a particular cell or cell type in a specific biological environment, its interconnections with the surrounding environment, and the roles that individual phenotypes play in healthy and diseased tissue function.
Key cells may be present in small numbers and produce infrequent and weak signals that get diluted and lost during averaging. For example, circulating cancer cells are rare but important, since they play a key role in cancer metastasis. Measuring gene expression within individual circulating cancer cells will hopefully shed light on cancer dissemination and metastasis.
“Single-cell mRNA and genomic analysis have already became a reality,” adds Dr. Wang, who will be speaking at Select Bioscience’s “Single Cell Analysis Congress” in May. “Proteomics and metabolomics experienced more challenges, which may be resolved by combining extremely efficient sample manipulation and highly sensitive detection. In that regard, micro-/nanofluidics interfaced with mass spectrometry (MS) could be a promising combination for single-cell proteomic analysis.”
Dr. Wang and colleagues have developed special multinozzle emitters for MS. Each emitter consists of a parallel silica nozzle array. These emitters could be linked to microfluidic circuits on one side and MS on the other side, thus forming an integrated lab-on-a-chip system with potential for future single-cell proteomics and metabolomics.