The molecule that determines cell fate

September 5, 2006

Brussels, 04 Sep 2006

Scientists have uncovered a group of molecules that controls the numbers and types of blood cell in the body. Defects in this system frequently lead to leukaemia and other diseases. The researchers hope their findings will contribute to our understanding of the intracellular processes that can lead to cancers. Scientists identified a number of molecular pathways in cells which control major biological processes. They are usually switched on and off by external factors, helping cells respond to their environment. One, the 'Wingless' pathway is found in almost all animals, where it plays a fundamental role in the development of tissues and organs. It also manages stem cells; deciding when they should remain as stem cells and when they should differentiate into other types of cell.

In the current study, researchers from the European Molecular Biology Laboratory (EMBL) and the University of Lund in Sweden investigated what happens when the Wingless pathway is too active in blood stem cells in mice. Their findings are published in the latest edition of Nature Immunology.

'We modified one element of the pathway, a protein called beta-catenin, so that it was stuck in 'transmission mode',' explained Peggy Kirstetter of the EMBL. '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.'

When the pathway is working normally, stem cells go through several steps before becoming fully differentiated blood cells. When the researchers stimulated the pathway, several types of blood cell disappeared completely, while others had their development blocked at various stages of differentiation. In mouse bone marrow, some types of stem cell disappeared, while others were too frequent.

The researchers' results show that beta-catenin plays a key role in determining whether blood cells form or not. Furthermore, beta-catenin seems to make cells take decisions about their fate before they leave the stem cell compartment in the bone marrow.

Claus Nerlov of the EMBL explained the implications of his team's findings. 'We know there are strong connections to cells' decisions to divide, to develop, or to die,' he said. 'If cells don't commit themselves to the right developmental path at the right time, they're very likely to die or to begin and inappropriate type of reproduction. Acute leukemias and other forms of cancer cells derive from defects such as this. Understanding the processes by which they form will require pinpointing the forks in the road where things go wrong.'

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