Stem cells hold a tremendous amount of research promise. At one time, obtaining them seemed to be a nearly insurmountable challenge, until a process was invented by Gladstone Senior Investigator Shinya Yamanaka, MD, Ph.D. After exposing skin cells to four specific proteins, stem cells will form. Now, investigators at Gladstone have made stem cells from mouse skin cells using another powerful technique - CRISPR gene editing. This method may be a more straightforward tool for some of the many potential applications of stem cells. The findings have been reported in Cell Stem Cell.
"This is a new way to make induced pluripotent stem cells that is fundamentally different from how they've been created before," noted author Sheng Ding, Ph.D., a senior investigator at Gladstone. "At the beginning of the study, we didn't think this would work, but we wanted to at least try to answer the question: can you reprogram a cell just by unlocking a specific location of the genome? And the answer is yes."
Pluripotent stem cells have the ability to become almost any type of cell. As such, they hold a lot of potential uses in the clinic. Conditions like blindness, heart failure, and Parkinson's disease might be treated by these cells, which also have many applications in the laboratory.
In the Nobel-prize winning finding, transcription factors, which regulate gene expression, turned skin cells into what was named induced pluripotent stem cells (iPSCs). In an update to that work, a chemical cocktail created the necessary changes. In the latest research, stem cells were made from skin cells by using CRISPR to induce changes in gene expression.
"Having different options to make iPSCs will be useful when scientists encounter challenges or difficulties with one approach," said Ding, who is also a professor of pharmaceutical chemistry at the University of California, San Francisco. "Our approach could lead to a simpler method of creating iPSCs or could be used to directly reprogram skin cells into other cell types, such as heart cells or brain cells."
For this work, the researchers used CRISPR to target two genes, Sox2 and Oct4. Those genes are known to control the expression of genes related to stem cell development. Through gene editing targeting a single location, they were able to initiate a chain reaction that reprogramed the cells and turn them into iPSCs. This way may be much simpler than altering transcription factors, which can affect hundreds or thousands of genes.
"The fact that modulating one site is sufficient is very surprising," Ding noted. "Now, we want to understand how this whole process spreads from a single location to the entire genome."
Learn more about the potential clinical applications of stem cells from the video above, featuring Yamanaka.
Sources: AAAS/Eurekalert! Via Gladstone Institutes, Cell Stem Cell
