PUBLIC RELEASE DATE:

13-Nov-2014

Contact: Krista Conger kristac@stanford.edu 650-725-5371 Stanford University Medical Center @sumedicine

A protein that plays a critical role in preventing the development of many types of human cancers has been shown also to inhibit a vital stem cell property called pluripotency, according to a study by researchers at the Stanford University School of Medicine.

Blocking expression of the protein, called retinoblastoma, in mouse cells allowed the researchers to more easily transform them into what are known as induced pluripotent stem cells, or iPS cells. Pluripotent is a term used to describe a cell that is similar to an embryonic stem cell and can become any tissue in the body.

The study provides a direct and unexpected molecular link between cancer and stem cell science through retinoblastoma, or Rb, one of the best known of a class of proteins called tumor suppressors. Although Rb has long been known to control the rate of cell division, the researchers found that it also directly binds and inhibits the expression of genes involved in pluripotency.

"We were very surprised to see that retinoblastoma directly connects control of the cell cycle with pluripotency," said Julien Sage, PhD, associate professor of pediatrics and of genetics. "This is a completely new idea as to how retinoblastoma functions. It physically prevents the reacquisition of stem cellness and pluripotency by inhibiting gene expression."

Marius Wernig, MD, associate professor of pathology, said, "The loss of Rb appears to directly change a cell's identity. Without the protein, the cell is much more developmentally fluid and is easier to reprogram into an iPS cell."

Wernig and Sage, both members of the Stanford Cancer Institute, share senior authorship of the study, which will be published online Nov. 13 in Cell Stem Cell. Postdoctoral scholar Michael Kareta, PhD, is the lead author.

Tumor Suppressor

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Tumor suppressor also inhibits key property of stem cells, Stanford researchers say