CISSTEM · Cis-regulatory logic of the transcriptional control in neural stem cells

Neural stem cells (NSCs) have emerged as a major topic in neurobiology. The persistence of multipotent cells in the adult mammalian brain offers a realistic chance for the treatment of neurodegenerative diseases. It is thus crucial to understand NSCs from as many as possible angles (e. g. cellular and molecular biology), in order to better isolate and successfully manipulate them. CISSTEM presents a post-genomic systems biology approach, taking advantage of new computational and experimental tools to address the specification and maintenance of NSCs at the transcriptional/epigenetic level. CISSTEM is designed to unravel the basic principles of gene regulation in NSC, with a focus on cis-regulatory modules (CRMs). To do so we follow a multidisciplinary approach tightly interconnecting computational prediction and experimental validation in vitro and in vivo using different vertebrate models systems. Major intermediate objectives of this project are the prediction of relevant elements and the identification of the temporal, spatial and quantitative activities of predicted conserved regulatory motifs associated with NSC expressed genes. To achieve this goal, CISSTEM will i) Develop computational tools and resources for the in silico identification of CRMs and transcription factor binding sites (TFBSs) ii) Identify genomic regions functionally active in the NSC through direct mapping of DNase I hypersensitivity sites. Putative functional annotation to these sites will be implemented and conduct direct CRM prediction of the identified regions iii) Identify motifs/signatures over-represented in distal elements found around NSC expressed genes iv) Identify the elements acting as transcriptional enhancers and define their pattern of activities in different neural cell lines and in vertebrate animal model systems v) Disseminate the results of the project to the research community, biotech/pharmaceutical companies and the general public