Ramsköld, D. et al. Nat. Biotechnol. 30, 777–782 (2012).

Although the genome of all cells in a given organism is largely the same, the transcriptome varies even within cells of the same tissue. Understanding this heterogeneity in gene expression will shed light on many developmental and disease processes but is technically challenging, even in the age of high-throughput RNA sequencing (RNA-seq). With their 'Smart-seq' method, Ramsköld et al. improve on previous protocols for single-cell RNA-seq, achieving balanced coverage across full transcripts rather than just the 3' ends of mRNAs. The researchers characterized the effect of low RNA input on the sensitivity of the method and its ability to detect differential expression. When applied to circulating tumor cells in a melanoma patient, Smart-seq yielded interesting leads for potential biomarkers.