New Cell Plasticity Regulation Method Uses CDK8 Inhibition

Scientists have discovered a new method that allows for cell plasticity regulation by inhibiting CDK8. The approach—developed by researchers from the Cellular Plasticity and Disease Laboratory at the Institute for Research in Biomedicine (IRB Barcelona)—focuses on gene expression mechanisms, does not affect cell viability, and is completely reversible, according to the research team. Their findings were published in Nature Cell Biology. 

"The identity of each cell type is defined by a particular gene expression program. What makes plastic cells special is that, in addition to their identity genes, they can express at low levels genes belonging to other cell identities. This sort of background noise is what allows them to change identity at a given time, and what was once background noise becomes the dominant genetic program," explains lead researcher Manuel Serrano.

Having the capacity to regulate cell plasticity can have many advantages in a biomedical research context as it allows researchers to study all the processes in which plasticity is a key element, such as cancer and embryo development. The present study has focused on embryonic stem cells. Their plasticity  makes them highly attractive for cell therapy applications. However, this very same plasticity poses a real challenge when it comes to culturing these cells in the lab.

"We have observed that CDK8 inhibition strengthens the expression of genes that determine cell identity, and this occurs at the expense of switching off the "background noise" of alternative identities. So the cells are fixed in a specific identity and they lose their plasticity," says Cian J Lynch, first author of the study. 

With respect to implications for oncology, "Cell plasticity is known to be a key factor underlying resistance to chemotherapy. By blocking cell plasticity, we hope to improve reactions to chemotherapy by achieving more homogeneous and lasting responses," Serrano concludes.