US research offers new insight into cell development and cancer
31 December 2012
Stem cells as known to the lay person are cells capable of transforming into any type of cell in the body, but scientists are trying to unravel the mechanism of the transformation. They are interested in understanding how stem cells are capable of being programmed down a defined path to contribute to the development of a specific organ like a heart, lung, or kidney.
Researchers at the University of North Carolina at Chapel Hill School of Medicine have uncovered the epigenetic signals function that determine the ultimate fate of a stem cell. The study, published on 27 December 2012 in the journal Molecular Cell, points to a unique class of proteins called polycomb-like proteins, or PCLs, as bridging molecules between the "on" and "off" state of a gene.
While all of these specialised cells share the same genetic information encoded in our DNA, it is now becoming quite clear that information outside the genome, called epigenetics, played a key role in the orchestratation of the reprogramming of a stem cell down a defined path. Although it was understood that epigenetics was responsible for turning genes "on" and "off" at defined times during cellular development, the precise mechanisms controlling this delicate process was yet to be fully understood.
According to Greg Wang, senior author of the study and assistant professor of biochemistry and biophysics at the UNC School of Medicine, and a member of UNC Lineberger Comprehensive Cancer Center, the finding had important implications for both stem cell biology and cancer development, as the same regulatory circuits controlled by PCL's in stem cells were often misregulated in tumors.
According to the study, led by postdoctoral research fellows Drs Ling Cai and Rui Lu in the Wang lab, and Scott Rothbart, a Lineberger postdoctoral fellow in the lab of Dr Brian Strahl, associate professor of biochemistry and biophysics in the UNC School of Medicine and a member of UNC Lineberger Comprehensive Cancer Center, PCLs interacted with an epigenetic signal associated with genes that are turned on to recruit a group of proteins called the PRC2 complex which then turn genes off.
Wang said in stem cells, the PRC2 complex turned genes off that would otherwise promote reprogramming into specialised cells of organs like the heart or lungs.
Additionally, elevated levels of PRC2 had been found in cancers of the prostate, breast, lung, and blood, and pharmaceutical companies were already developing drugs to target PRC2. Wang and colleagues identified the same mechanisms controlling PRC2 function to be responsible for causing cancers in humans.
Wang said the identification of a specific PCL in controlling PRC2 in cancer cells suggested scientists may be able to develop drugs targeting this PCL to regulate PRC2 function in a more controlled manner that may maintain PRC2 function in stem cells while inhibiting it in the tumor.