Mechanism That Maintains Stem Cell Readiness Identified

 An immune-system receptor plays an unexpected but crucially important role in keeping stem cells from differentiating and in helping blood cancer cells grow according to new research. The family of proteins investigated in the research could help open a new field of biology integrating immunology with stem cell and cancer research.

“Cancer cells grow rapidly in part because they fail to differentiate into mature cells. Drugs that induce differentiation can be used to treat cancers,” said Dr. Chengcheng “Alec” Zhang, assistant professor in UT Southwestern’s departments of physiology and developmental biology. “Our research identified a protein receptor on cancer cells called a classical immune inhibitory receptor that inhibits differentiation. Knowing the identity of this protein should facilitate the development of new drugs to treat cancers.”

The protein receptor, classical immune inhibitory receptor, is known to maintain stemness of normal adult stem cells and to be important in the development of leukemia. Stemness refers to the blood stem cells’ potential to develop into a range of different kinds of cells as needed, for instance to replenish red blood cells lost to bleeding or to produce more white blood cells to fight off infection. Once stem cells differentiate into adult cells, they cannot go back to being stem cells.

Prior to this research, no high-affinity receptors had been identified for the family of seven proteins called the human angiopoetic-like proteins. These seven proteins are known to be involved in inflammation, supporting the activity of stem cells, breaking down fats in the blood, and growing new blood vessels to nourish tumors.

The researchers found that the human immune-inhibitory receptor LILRB2 and a corresponding receptor on the surface of mouse cells bind to several of the angiopoetic-like proteins. Further studies showed that two of the seven family members bind particularly well to the LILRB2 receptor and that binding exerts an inhibitory effect on the cell, similar to a car’s brakes.

Inhibition keeps stem cells in their stem state. They retain their potential to mature into all kinds of blood cells as needed but they don’t use up their energy differentiating into mature cells. That inhibition helps stem cells maintain their potential to create new stem cells because in addition to differentiation, self-renewal is the cells’ other major activity, Dr. Zhang said. He stressed that the inhibition doesn’t cause them to create new stem cells but does preserve their potential to do so.

Related post. "Determining A Stem Cell's Fate," California Institute of Technology, April 2012.

Adapted from the UT Southwestern Medical Center announcement.