The Systems Biology of Stem Cells and Reprogramming (SyBoSS) project aims to research stem cell differentiation using a new type of approach. In contrast to single-gene hypothesis based research, systems biology allows us to derive a global picture, gaining information about all the interactions in the whole cell population. The study will yield comprehensive information about the whole range of interactions between genes and proteins, allowing us to compare different stages of development as stem cells give rise to different progeny of various cell types.
The particular focus will first be on comparing the simple embryonic type of cell, which could give rise to any cell type, with cells that are committed to producing only nerve cells. Recent work has shown that this commitment can be reversed in the laboratory, so that neural stem cells can be reprogrammed back to the totipotential embryonic state, once a critical “tipping point” is reached. The molecular interactions that affect this process are the focus of SyBoSS attention.
Genetic recombineering will be used to label or to eliminate particular gene products. A hit list of 300 potential targets has been drawn up, all of them major players in controlling cell function. The labels can be used to find out which other proteins and which genetic sequences interact together, by the use of sophisticated mass spectrometry and correlation with the known genetic sequences. Fluorescent labels attached to proteins can also be used for high-resolution microscopy to work out what makes the difference between an uncommitted cell and its differentiating progeny. All of the work will be done with mouse cells, although the implications for human stem cells are the basis for possible medical advances and better understanding of human diseases.
The vast amount of data that results from the SyBoSS experiments can be analysed using newly developed computer algorithms. These computational methods will be further developed during the project, to provide ways to model and depict the networks of interactions that are discovered.
Selected genes will be more intensively studied, and further studies are planned, to look at the development of nerve and later blood cells from committed stem cells. These studies should improve our understanding of how different tissues arise, and how flexible their characteristics might be.
Although Francis Stewart and Andreas Beyer cautiously refer to the obstacles facing use of reprogrammed cells to cure human conditions, they still enthusiastically hope for new impetus in the treatment of conditions such as cancer, brain damage and depression. The SyBoSS Project will take the first step towards this goal by creating a broad, comprehensive and also deep repository of knowledge as to how molecular interactions regulate cell behaviour.