Decades of Toil Yield Purified Protein

Multiplying like bunnies. Adding the Wnt protein to blood stem cells induces rapid proliferation (bottom).

After decades of painstaking effort, a team of scientists has purified a protein that stars in multiple cell dramas, from embryonic development to cancer. The protein, called Wnt, turns out to have a further power: It coaxes blood stem cells to divide briskly, prompting hope that Wnt might make it easier to experiment on stem cells and, someday, apply them in therapy.

The studies came out of two collaborating labs at Stanford University in California involved in seemingly disparate pursuits. In one, stem cell pioneer Irving Weissman, Tannishtha Reya, and their colleagues were struggling to boost the number of stem cells in a petri dish without letting them become different kinds of tissues. Producing lots of undifferentiated stem cells is crucial for learning how to direct the cells' development. Nearby, developmental biologist Roel Nusse and his lab members were wrestling with their own albatross, the signaling protein Wnt, which had resisted all attempts to purify it.

The "eureka" moment came when Nusse and postdoc Karl Willert determined that Wnt was hydrophobic--something its genetic sequence hadn't suggested. Wnt acquires its avoidance of water from a lipid molecule that latches onto it before it's shuttled out of the cell, the researchers found. Nusse's team shifted its purification plan to one commonly used for proteins bound to lipids, and successfully isolated a mouse Wnt protein.

With unadulterated Wnt in hand, the researchers added the protein to mouse stem cells from bone marrow, which generate a range of blood and immune cells. Over 1 week, Wnt-treated stem cells produced at least six times more daughter cells than did controls. Another set of experiments revealed that boosting levels of a protein triggered by Wnt, called -Catenin, had similar effects on the stem cells. And when those cells were infused into mice whose bone marrow had been wiped out with radiation, they rebuilt the animals' immune system. Both Nusse's and Weissman's papers appear online today in Nature.

Others are enthusiastic about the results. "This is one of the first times that you see amplification of stem cell populations, which is what everyone's been looking for," says Leonard Zon, a geneticist at Children's Hospital Boston. Adds Guy Sauvageau, a stem cell biologist at the University of Montreal in Canada: "We're close to being able to tell clinical people that yes, they now have proteins that will allow the expansion" of stem cells.

Related sites
The Wnt home page at Stanford
Stem cell primer from NIH
Roel Nusse lab home page
Irving Weissman home page

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