Genomics: The single life - Sequencing DNA from individual cells is changing the way that...

NATURE NEWS ^ | 31 October 2012 | Brian Owens

[neverdem]

Sequencing DNA from individual cells is changing the way that researchers think of humans as a whole.

All Nicholas Navin needed was one cell — the issue was how to get it. It was 2010, and the postdoctoral fellow at Cold Spring Harbor Laboratory in New York was exploring the genetic changes that drive breast cancer. Most of the cancer-genome studies before then had ground up bits of tumour tissue and sequenced the DNA en masse, giving a consensus picture of the cancer’s genome. But Navin wanted to work out the sequence from individual cells to see how they had mutated and diverged as the cancer grew.

He ran into trouble almost immediately. “Cells like to stick together,” he says. He tried the most advanced microdissection techniques, which use robots to peel cells apart or suck them into the tips of hair-thin glass pipettes. But he could never be sure that asecond cell hadn’t come along for the ride. Eventually, he settled on using chemicals to dissolve the cell’s outer membrane and release the dense nucleus. Then he separated out the nucleus using an automated cell sorter, and extracted its DNA. He repeated the process for around 100 cells, and the sequences he obtained revealed how the tumour had evolved from a few rogue cells into a complex mélange of genetically distinct ones1.

The ability to sequence 100 human cancer genomes was unthinkable a decade ago, and it is still a remarkable feat. Technology has moved apace, dramatically reducing costs and making genome sequencing fairly routine. But most human genomes, cancer or otherwise, are still sequenced from DNA extracted from multiple cells, which misses differences between cells that could be crucial in controlling gene expression, cell behaviour and drug response.

“People are becoming very interested in what is the variation...”