EU project partners uncover role of oxygen in cell development
Researchers working on EU funded EuroStemCell project at Stockholm's Karolinska Institute have made a discovery about the role played by oxygen in cell development that may shed light on the processes at work in tumour development. The research, published in the November issue Developmental Cell, also has implications for growing stem cells in the laboratory.
'Understanding how the body precisely controls stem cell fate is a key goal of stem cell research,' says EuroStemCell researcher Urban Lendahl.
Until now, scientists knew that stem cells could grow more easily as undifferentiated cells when oxygen levels are reduced, but could not say why. The Karolinska scientists have cleared this up, explaining the molecular basis of this phenomenon, and uncovering the role of the Notch signalling pathway in the process.
The study of the mechanisms governing the development of multicellular organisms is an attempt to explain how an undifferentiated precursor cell responds to developmental signals and progresses to the next developmental state. Acquisition of specific cell fates during development depends on an intricate interplay of signalling pathways. Also, many human pathologies involve the inability of cells to properly respond to developmental signals.
One evolutionary conserved pathway, among the most ubiquitous cell-to-cell signalling routes in the animal kingdom, is the Notch pathway. This pathway is involved in an uncountable number of developmental pathways, and plays an important role in many human diseases, ranging from cancer to strokes. The Notch family of proteins is a critical regulator in the process of differentiation - where stem cells take on more specialised functions.
'Our finding that Notch signalling mediates the effect of reduced oxygen levels on brain and muscle stem cells will help researchers working on these cells to replicate the body's mechanisms in the lab. This is an important prerequisite for developing safe and effective clinical applications,' explains Dr Lendahl.
Moreover, the link between Notch and reduced oxygen levels may prove useful in cancer research. Certain types of tumour develop because of mutations in the machinery that sense reduced levels of oxygen (hypoxia) in the body. The findings by the EuroStemCell partners may provide new insights into the molecular processes at work as these tumours develop, opening up possibilities for intervening in these processes.
EuroStemCell is an Integrated Project with funding of 11.9 million euro for its four-year duration under the 'life sciences, genomics, and biotechnology for health' section of the Sixth Framework Programme (FP6). The consortium brings together 14 partners, integrating a broad range of disciplines.
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Remarks: Reference document: Gustafsson M., Zheng X., Pereira T., Gradin K., Jin S., Lundkvist J., Ruas J.L., Poellinger L., Lendahl U., and Bondesson M. (2005) Hypoxia requires Notch signalling to maintain the undifferentiated cell state. Dev. Cell 9(5):617-28
Data Source Provider: EuroStemCell project
Document Reference: Based on information from the EuroStemCell project
Subject Index: Life Sciences; Medicine, Health; Scientific Research