The Notch effect steers stem cells into cells of the nervous system

11 April 2006
What have the researchers discovered, and why is this interesting? Embryonic stem cells have the potential to make all 200 cell types in the body. The challenge is to restrain this diversity and uncover the signals that commit stem cells to a single specialised function. have now established that Notch gives embryonic stem cells the critical push towards becoming cells of the nervous system.
	The researchers show that when Notch is activated in embryonic stem cells, up to 90% of the cells in the dish become nerve cells, shown in green (left). In any colony of embryonic stem cells, under normal conditions, many never become cells of the nervous system: they spontaneously change into other cell types or remain as embryonic stem cells.
The Notch effect can be observed in both mouse and human embryonic stem cells, and can be created without any recourse to genetic engineering - all it takes is the presence of Notch activating signals in the cells that stem cells grow on. As individual embryonic stem cells become specialised, they communicate with those around them. Notch is a major means of communication, and has, according to Dr Lowell, "a domino effect: once it is switched on in a small group of cells, it sets off a wave of Notch activation in neighbouring cells, directing them all to become cells of the nervous system." This research has far-reaching implications for other aspects of stem cell research. Dr Lowell adds, "We expect our findings to shed light on how to make other types of cell, such as muscle or pancreatic cells. If we can identify the processes that Notch blocks in embryonic stem cells we will have a handle on how to get them started, and so drive embryonic stem cells to become other types of cell that are more difficult to grow in the lab". Says Professor Austin Smith, leading the Edinburgh team and coordinating the EuroStemCell consortium, "This discovery gives us another method to generate pure populations of nerve cells - so important for drug screening, disease modelling and potential cell therapies." View full paper http://dx.doi.org/10.1371/journal.pbio.0040121 How did EuroStemCell collaboration make his research possible? This study reveals how embryonic stem cells use Notch as a means of communication. Scientific communication and exchange, made possible by the concentration of stem cell expertise in the EuroStemCell consortium, has also been critical in the development of this work. Colleagues at the Wellcome Trust Sanger Institute developed antibodies that allowed researchers to detect Jagged, a binding partner (ligand) for Notch in cell-to-cell communication. Urban Lendahl's laboratory provided Notch expertise and reporters. Institut Pasteur investigator Ana Cumano provided a cells expressing Notch ligand. Another EuroStemCell partner, Stem Cell Sciences, has exclusively licensed the technology described in this paper. Back to Project News