Studies of the transcriptome rarely take into account the structural context within a living cell. In the August 2 Science, Jeffrey Levsky and colleagues describe a sophisticated approach that monitors mRNA synthesis of multiple genes within single cells (Science 2002, 297:836-840).
The authors prepared oligomer DNA probes, each tagged with a distinct fluorophore, and combined them to create gene-specific spectral barcodes. They used these probes to follow the transcription of 11 genes in starved and serum-stimulated cells by FISH (fluorescence in situ hybridization). They were able to measure expression in terms of signal intensity and the number of transcribed alleles. Some genes showed strong co-regulation, implying similar regulatory mechanisms. Comparison with microarray data ("FISH and Chips") highlighted the differences between single-cell recordings and global measurements of entire cell populations, and differences between the rate of transcription and the abundance of mRNA.