Stem cells hold promise for regenerative medicine because they can turn into any type of tissue, but the need to harvest them from human embryos has stymied research in this field. One way around this issue is to turn back the clock on differentiated cells, reverting them to a stage before they grew into a specific type (…)
Treatments and research using this technology have been slow to develop, however. Even though techniques that turn adult cells into these iPS cells have existed for a decade, the process is not foolproof. After reverting to their pluripotent state, these cells don’t always correctly differentiate back into adult cells.
Penn bioengineers Jennifer Phillips-Cremins, an assistant professor in the Department of Bioengineering in the School of Engineering and Applied Science, and Jonathan Beagan, a graduate student in her lab, have now discovered one of the potential reasons why: The reversion process does not always fully capture the way a cell’s genome is folded up inside its nucleus (…)
By applying experimental and computational techniques that the Cremins lab has developed, her group was able to identify folding patterns in iPS cells that had previously been unseen.
“Previous methods provided data analogous to an old television, with large, black-and-white pixels,” Phillips-Cremins says. “One could generate a blurry image and tell there was a person on the screen, but it would be difficult to parse finer scale facial features. We employed methods to create high-resolution maps of genome folding, so we could distinguish detailed topological features and evaluate their similarities and differences among traditional embryonic stem cells, iPS cells, and mature, differentiated cells” (…)
The researchers found that traditional embryonic stem cells and more mature neural stem cells from the brain had strikingly different genome folding patterns. Surprisingly, however, the genetic material from iPS cells did not fold in a manner that perfectly resembled traditional embryonic stem cells, but instead exhibited traces of the 3-D configurations of the brain cells from which they were derived (…)