It was once thought that each cell in a persons body possesses the same DNA code and that the particular way the genome is read imparts cell function and defines the individual. For many cell types in our bodies, however, that is an oversimplification. Studies of neuronal genomes published in the past decade have turned up extra or missing chromosomes, or pieces of DNA that can copy and paste themselves throughout the genomes. The only way to know for sure that neurons from the same person harbor unique DNA is by profiling the genomes of single cells instead of bulk cell populations, the latter of which produce an average. Now, using single-cell sequencing, Salk Institute researchers and their collaborators have shown that the genomic structures of individual neurons differ from each other even more than expected. The findings were published November 1 in Science. Contrary to what we once thought, the genetic makeup of neurons in the brain arent identical, but are made up of a patchwork of DNA, says corresponding author Fred Gage, Salks Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease. A good bit of our study was doing control experiments to show that this is not an artifact, says Gage. We had to do that because this was such a surprise -- -- finding out that individual neurons in your brain have different DNA content. The group found a similar amount of variability in CNVs within individual neurons derived from the skin cells of three healthy people. Scientists routinely use such induced pluripotent stem cells (iPSCs) to study living neurons in a culture dish. Because iPSCs are derived from single skin cells, one might expect their genomes to be the same. The surprising thing is that theyre not, says Gage. There are quite a few unique deletions and amplifications in the genomes of neurons derived from one iPSC line. Interestingly, the skin cells themselves are genetically different, though not nearly as much as the neurons. This finding, along with the fact that the neurons had unique CNVs, suggests that the genetic changes occur later in development and are not inherited from parents or passed to offspring.
Posted on: Mon, 04 Nov 2013 01:45:53 +0000
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