Excessive stimulation of bone marrow stem cells in mice leads to severe anemia and ultimately death, according to research to be published in the October issue of Nature Immunology.
Hematopoietic stem cells residing in the bone marrow give rise to all blood cells circulating in the body. To ensure a lifelong supply of blood cells, these stem cells must continuously self-renew. Previous work revealed stem cells require a signaling molecule called Wnt to activate beta-catenin, a protein involved in self-renewal. Research from two groups shows that excessive beta-catenin signals lead instead to a loss of stem cells and problems in blood cell development. Mice expressing a mutant form of beta-catenin, engineered to be permanently switched on, died at a very young age due to defects in blood cell production. These findings suggest therapeutic manipulation of bone marrow stem cells via Wnt signals to achieve increased blood cell production needs to be finely balanced to avoid too much of a good thing.
Claus Nerlov (EMBL Mouse Biology Unit, Monterotondo, Italy)
Achim Leutz (Max-Delbrueck-Center for Molecular Medicine Tumorigenesis and Differentiation, Berlin, Germany)
Abstracts available online:
(C) Nature Immunology press release.
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