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Blood cells have limited lifespans, which means that they must be continually replaced by calling up reserves, and turning these into the blood cell types needed by the body. Claus Nerlov and his colleagues at the European Molecular Biology Laboratory (EMBL) unit in Monterotondo, Italy, in collaboration with researchers from Sten Eirik Jacobsen's laboratory at the University of Lund in Sweden, have now uncovered how an intracellular communication pathway contributes to this process. Because defects in such pathways and in the development of stem cells frequently lead to leukemia and other diseases, the work should give researchers a new handle on processes within cells that lead to cancer. The work is published in this week's online issue of Nature Immunology.

Over the past decades, molecular biologists have identified several pathways ?sequences of molecules which manage the flow of information within the cell ?responsible for major biological processes. One of these, the "Wingless" pathway, plays a vital role in shaping tissues and organs in developing embryos of nearly all animal species. It also helps organisms manage stem cells, by keeping them on hold and preventing their differentiation until the right time. Such pathways are usually switched on and off by external stimuli that help cells respond properly to the environment. Now Peggy Kirstetter and other members of Nerlov's lab have shown what happens when Wingless is too active in hematopoietic stem cells in mice.

"We modified one element of the pathway, a protein called beta-catenin, so that it was stuck in 'transmission mode,'" Kirstetter says. "This created cells in which the pathway was always switched on. We've known that Wingless contributes to blood differentiation, but didn't know how the signals were being transmitted within the hematopoietic stem cell."

The modified protein had dramatic effects. Usually, most cells undergo numerous transitional stages on their way from stem
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Source:European Molecular Biology Laboratory


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