Good for something: prion protein maintains stem cells.

The same protein that, in an altered shape, causes mad cow disease and other neurodegenerative disorders maintains the body's cache of blood-producing stem cells, a new study suggests.

Called the prion protein, or PrP, it's scattered throughout the body in mammals. When, in rare occurrences, PrP becomes misshapen, it causes neurodegenerative diseases in cows (SN: 1/10/04, p. 19), deer (SN: 1/28/06,p. 52), people (SN: 10/4/97, p. 212), and other species. However, researchers haven't been sure what function the normal protein performs.

"For years, we've wondered why evolution has preserved this protein, what positive role it could possibly be playing," says Susan Lindquist of the Whitehead Institute for Bio-medical Research in Cambridge, Mass.

While studying blood-producing stem cells in mouse fetal tissue, Lindquist's colleague Cheng Cheng Zhang noticed that PrP was present on the cells' surfaces. To determine whether the protein plays a part in how stem cells operate, Zhang, Lindquist, and their Whitehead colleagues Andrew Steele and Harvey Lodish compared the blood and the blood-producing stem cells found in bone marrow in normal mice and in mice missing the gene for PrP. They observed no differences between the two sets of samples.

However, the researchers quickly noticed a distinction when they subjected stem cells to the stress of bone marrow transplants. The scientists moved bone marrow from normal and PrP-deficient mice into similar mice that had been irradiated to kill off their blood-producing stem cells. After the stem cells in the transplanted bone marrow became established and reproduced, the scientists repeated their procedure, transferring bone marrow from these recipients into new irradiated mice.

In normal mice, the researchers found that each new bone marrow transplant was as effective as the previous one, and all the recipients thrived. However, in the mice without PrP, the stem cells gradually lost their capacity to reconstitute themselves with each subsequent transplant.

When the researchers inserted the gene for PrP into stem cells in the bone marrow taken from mice without PrP, the marrow became as hardy as that from normal mice. The scientists report their results in an upcoming Proceedings of the National Academy of Sciences.

Lodish notes that previous studies investigating PrP's function may have missed this role because they didn't provide the extreme stress that puts blood-producing stem cells to the test. "When there's loss of blood, a massive infection, or a bone marrow transplant, that's where these stem cells spring into action," he says.

The results are "interesting and novel, because no one had studied the role of prion protein in this type of cell," notes Andrea LeBlanc of McGill University in Montreal, who investigates these proteins.

However, she says, the experiments don't explain why mice without the PrP gene can survive to old age, given that blood-producing stem cells wear out over a lifetime of normal stress. "If these mice had an incapacity to proliferate cells and were prone to stress," LeBlanc argues, "you'd assume that they would die or have problems in late life, and they don't."