Whilst flow cytometry remains the gold standard tool for single cell characterisation, recent advances are increasing our ability to delve deeper into cellular heterogeneity. These advances extend cell characterisation beyond immunodetection coupled with fluorescence or metal isotopes to highly-parallel transcriptional phenotyping, entering the emerging field of Genomic Cytometry.
Analysing thousands of parameters in each cell simultaneously, single-cell RNAseq systems have arisen as a powerful method to characterise cell diversity in complex tissues. In the last two years we have developed extensive experience in high dimensional characterisation of single cells, both with droplet based SCRNAseq systems, as well as high dimensional fluorescent panels for the Symphony A5.
Here we highlight some of the major changes that have occurred in the cytometry field over the past few years and describe the emergence of what we are calling Genomic Cytometry. That is, the measurement of cells using nucleic acid sequencing. As we show, Genomic Cytometry not only allows the detection of cell intrinsic nucleic acids but through smart molecular approaches nucleic acid sequence can be used as a surrogate measure for many other cell characteristics, including high dimensional epitope detection.
To illustrate the power of genomic cytometry we compare data obtained using high throughput whole transcriptome using droplet-based systems (Dropseq and Indrop) and targeted single-cell RNASeq (BD Rhapsody) showing how the high dimensional (25 plus colour) fluorescent panels complement genomic approaches. Finally we discuss how oligo labelled antibodies are set to push the dimensionality barrier for epitope detection well beyond what we currently think is possible.