Simulating Stem Cells for Tomorrow's Treatments

Stem cells are a hot subject of medical research in recent years. Perhaps the most interesting property that these cells possess is their ability to differentiate from pluripotent cells into specialists.

We decided to engineer a network that mimics this phenomonon of differentiation.

In 2014, iGEMuOttawa undertook a similar project, where we implemented a network called a tri-stable switch. Based on Sui Huang's 2009 paper this network allows the expression of one of two genes, A and B, that represent two differentiated states. But there is also a third state, where both A and B are expressed. This third state represents the pluripotent cell.

An example of a tri-stable switch in nature. SA, SB and SC stand for state A, B and C, where state C is the undifferentiated AB state. Figure from Huang et al. 2007.

However, our mathematical models have revealed that the dynamics of the genetic network we built cannot yield the third, pluripotent state. Thus, with new data from our model, we have completely re-designed the network with new dynamics to hopefully achieve tristability.

Our new genetic network.

Although our network this year still did not achieve tristability, we have discovered new methods of gene regulation by modifying promoters with transcription factor binding sites. With time, it will eventually be possible to costruct a genetic network that implements the tri-stable switch. This research will shed light on the inner workings of natural stem cells, and perhaps allow synthetic stem cells to be engineered in next-generation therapies.