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• What is neural stemness?• Why is it important?• What are the molecular
signatures of neural stemness?
• What are the regulatory networks that control neural stemness?
Neural stemness
“Bottom-up” – single gene (REST)•Map genome binding sites•Map loci that are transcriptionally and/or epigenetically regulated•Knock gene out in cells and mice & look at effect on ‘function’•But – which aspects of transcriptional and epigenetic regulation are critical to this function?
Looking for networks“Top-down” – networksIsolating defined regulatory modules
Inferring regulatory modules
Challenges• “Bottom-up”: what does a network
look like from a single gene’s point of view
• “Top-down”: what does a network look like from a global point of view
• Integrate all the ‘omes to enable a network to include knowledge of the transcriptome, epigenome and proteome
• Find a way to conceptualise, model and test such networks
• Prove the value by manipulating a neural stem cell at will to any desired outcome