Prions and Stem Cells

The prion responsible for "mad cow" disease apparently has a role in maintaining adult stem cells. The research findings are reported in the Proceedings of the National Academy of Sciences this week.

Zhang teamed up with the Lindquist lab's graduate student Andrew Steele, an expert in prions, to discover what role PrP might play in stem cell biology. Zhang and Steele took bone marrow from mice in which PrP had been knocked out, and transferred that marrow into normal mice whose blood and immune systems had been irradiated. The new bone marrow took hold, and these mice flourished, although all their blood cells lacked PrP. Zhang and Steele continued the experiment, this time taking bone marrow from the newly reconstituted mice, and transplanting it into another group of mice. They repeated this process again and again--transplanting bone marrow from one group of mice to another like passing a baton.

Soon they noticed that with each subsequent transplant, the stem cells began to lose their ability to reconstitute. Eventually, the scientists ended up with mice whose hematopoietic stem cells completely lacked the ability to generate new cells. However, in the control group, where they mimicked the experiment with bone marrow abundant with PrP, each transplant was as good as the next, and at no point down the line did stem cells lose their efficacy.

"Clearly, PrP is important for maintaining stem cells," says Lodish. "We're not sure yet how it does this, but the correlation is obvious."