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Induced pluripotent stem cells reveal differences between humans and great apes


From left: Ahmet Denli, Carol Marchetto, Iñigo Narvaiza and Fred Gage

Scientists regularly use induced pluripotent stem cells (iPSCs) to model diseases using cells that would be otherwise difficult to obtain from a living person or animal. By adding a combination of four key factors, a skin cell can be made into an iPSC, which can then be coaxed into forming liver, lung and brain cells in a culture dish.

It's now also possible to compare iPSCs from humans to those of our closest living relatives—great apes. Recently, scientists working in the lab of Fred Gage, who holds the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease, took chimpanzee and bonobo skin cells and for the first time turned them into iPSCs.

"Comparing human, chimpanzee and bonobo cells can give us clues to understand biological processes, such as infection, diseases, brain evolution, adaptation or genetic diversity," says senior research associate Iñigo Narvaiza, who led the study with senior staff scientist Carol Marchetto and senior research associate Ahmet Denli.

In the study, published in Nature, the team found disparities in the regulation of jumping genes, or transposons—DNA elements that can copy and paste themselves into spots throughout the genome—between humans and non-human primate cells. Jumping genes provide a means to rapidly shuffle DNA and might be shaping the evolution of our genomes, the researchers say.

The group identified genes that are differentially expressed between iPSCs from humans and both chimpanzees and bonobos. To their surprise, two of those genes code for proteins that restrict a jumping gene called L1, which along with a handful of other jumping genes is abundant throughout our genomes. Compared with non-human primate cells, human iPSCs expressed higher levels of these restrictors.

Using L1 tagged with a fluorescent marker, the scientists found, as expected, that an excess of the two proteins dampened the mobility and reduced the appearance of newly inserted DNA in the non-human primate cells. These results suggested that L1 elements insert themselves less often throughout our genomes. Indeed, looking at genomes of humans and chimpanzees that had already been sequenced, they found that the primates had more copies of L1 sequences than did humans.

The new study provides proof of concept that iPSC technology can be used to understand some of the evolutionary differences between humans and non-human primates.