Shotgunning the messenger – Single-cell RNA sequencing

From Science by Alan Dove

New tools are helping scientists sequence and study RNA in unprecedented detail, but each technique has its own strengths and limitations.

At the turn of the 21st century, plummeting costs and rapidly advancing technology sent many scientists rushing to sequence DNA. The field of genomics blossomed, and organisms of all types had their complete genome sequences published. While sequencing genomes has now become routine, the resulting flood of DNA data hasn’t proved adequate to fully explain many of the phenomena biologists study.

How does a single genome give rise to all the cells in a complex organism? What genes do cancer cells turn on and off to escape the normal checks on their growth? How do lymphocytes respond to pathogens, and how do pathogens escape that response? Answering those questions requires drilling deeper into cellular information flows by sequencing and tracking the changes of the RNA transcripts produced from genomes.

But RNA is harder to study than DNA: It degrades easily and must be reverse-transcribed to accommodate most sequencing techniques. The transcripts of different genes also vary tremendously in abundance. Fortunately, researchers and laboratory suppliers have been steadily improving RNA sequencing tools, empowering the rapidly growing field of transcriptomics. As the technology advances, scientists are increasingly studying RNA changes within single cells, revealing entirely new levels of cellular behavior.

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