Mouse iPSCs were created in 2006 by Kazutoshi Takahashi and Shinya Yamanaka at Kyoto University in Japan, and human iPSCs soon followed----feats which earned Yamanaka the Nobel Prize in Physiology or Medicine last year. Now scientists regularly use 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 possible to not only model disease using the cells, but also to compare iPSCs from humans to those of our closest living relatives----great apes, with which we share a majority of genes----for insight into what molecular and cellular features make us human.
"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 Iņigo Narvaiza, who led the study with senior staff scientist Carol Marchetto at the Salk Institute in La Jolla. "Until now, the sources for chimpanzee and bonobo cells were limited to postmortem tissue or blood. Now you could generate neurons, for example, from the three different species and compare them to test hypotheses."
In the new study, published online October 23 in the journal Nature
, scientists 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 scientists say.
Working in the lab of Salk's Fred Gage, the Vi and John Adler Chair for Research on Age-Related Neurodegenerative Disease, Narvaiza, Marchetto and their colleagues identified genes that are differentially expressed between iPSCs from humans and both chimpanzees and bonobos.
To the group's surprise, two of those genes code for proteins that restrict a jumping gene called long interspersed element-1or L1, for short. Compared with non-human primate cells, human iPSCs expressed higher levels of these restrictors, called APOBEC3B and PIWIL2. "We weren't expecting that," Marchetto says. "Those genes caught our eyes, so they were the first targets we focused on."