Using CRISPR technology, researchers have generated authentic induced pluripotent stem cells. The approach offers a potentially simpler technique to produce iPSCs and provides important insights into the cellular reprogramming process, according to the Gladstone Institutes team that conducted the research.
"This is a new way to make induced pluripotent stem cells that is fundamentally different from how they've been created before," said author Sheng Ding, 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."
More than ten years ago, Gladstone senior investigator Shinya Yamanaka, discovered he could make stem cells, dubbed induced pluripotent stem cells (iPSCs), by treating ordinary skin cells with four key proteins. Building on this work, Ding and others previously created iPSCs by adding a cocktail of chemicals to the cells. The latest study, published yesterday in Cell Stem Cell, offers a third way to turn skin cells into stem cells by directly manipulating the cells' genome using CRISPR gene regulation techniques.
"Having different options to make iPSCs will be useful when scientists encounter challenges or difficulties with one approach," said Ding. "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."
Ding's team targeted two genes that are only expressed in stem cells and known to be integral to pluripotency: Sox2 and Oct4. Like transcription factors, these genes turn on other stem cell genes and turn off those associated with different cell types.
The researchers discovered that with CRISPR, they could activate either Sox2 or Oct4 to reprogram cells. In fact, they showed that targeting a single location on the genome was enough to trigger the natural chain reaction that led to reprogramming the cell into an iPSC.