Caspases are central to induced pluripotent stem cell transformation


University of Colorado Cancer Center researcher Chuan-Yuan Li, and his co-workers have discovered that caspase genes are the gatekeepers that can open the door to allow differentiated adult cells to regress to undifferentiated iPSCs. Caspase genes encode protein-degradation genes that initiate programmed cell death. Programmed cell death is an essential process in development, and in the maintenance of tissues, blood cells, and other physiological processes where cells must die and be replaced by other newly minted cells.
Li and his colleagues found that if they treated fully differentiated cells with chemicals that inhibit caspase and then treated them with genes that can cause them to become induced pluripotent stem cells (iPSCs), the fully differentiated cells refused to become iPSCs, even thought they were expressing the genes that normally drive cells to become iPSCs.
These experiments show that caspases are essential for the iPSC transformation. They do not drive the transformation, since Li and his co-workers tried placing extra caspase genes into cells without any iPSC transformation. Nevertheless, Li’s work shows that without functional caspase, iPSC formation does not occur, which makes it one of the central elements in iPSC formation.
Li stated that caspases seem to loosen up the built-in controls that make a cell differentiated or undifferentiated, just like a clutch allows a driver to switch gears while driving. Undifferentiated stem-like cells and differentiated cells from one person have the exact same genes. The difference between them is which genes are turned on or off. Caspases, therefore, could be the key to taking a cell and changing it back to its original state to become any kind of cell.
Li noted: “It is now becoming clear that caspases don’t just kill, but they can change the cell’s fate. They could be a mediator of epigenetic changes in multi-cellular organisms.”