After discovering it was possible to turn skin cells into stem cells using a combination of four transcription factors, researchers at the Gladstone institute have been investigating other methods that can be used to manufacture pluripotent stem cells.
Pluripotent stem cells can be turned into almost any cell type in the body, so they are extremely valuable to researchers for studying diseases and have many clinical uses. However, obtaining stem cells from donors can be costly, especially in the numbers required for therapies and medical research. Reprogramming cells to create stem cells in the lab offers many advantages.
The first success at Gladstone Institute came in 2006, when Dr. Shinya Yamanaka and his team reprogrammed skin cells and turned them into induced pluripotent stem cells (iPSCs) in the lab. Four transcription factors were added to skin cells which altered gene expression, activating those that are normally only active in stem cells. The result was the transformation of skin cells into stem cells.
Building on that research, Dr. Sheng Ding at the Gladstone Institute discovered it was possible to turn skin cells into stem cells using a chemical approach. Now Ding and fellow researchers have discovered a third approach, this time using CRISPR-Cas9 to active the stem cell genes.
The two genes targeted by the researchers are known as Sox2 and Oct4. Both of these genes are only expressed in stem cells and play an integral part in the pluripotency of the cells. Using the CRISPR-Cas9 gene editing tool the researchers were able to activate these genes, reprogramming skin cells and turning them into IPSCs.
The researchers claim the CRISPR approach is far simpler that the other two methods used to create iPSCs. By targeting a single location on the genome, they triggered a chain reaction that caused the cells to be reprogrammed into iPSCs
“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,” said Ding. Ding said, “Now, we want to understand how this whole process spreads from a single location to the entire genome.”
The research paper – CRISPR-Based Chromatin Remodeling of the Endogenous Oct4 or Sox2Locus Enables Reprogramming to Pluripotency – has recently been published I the Journal Cell Stem Cell.