Objective
The objectives of this project are to characterize central nervous system (CNS) stem cells and to gain insights into how their differentiation to neurons can be controlled. Neurons and glial cells in the adult CNS are derived from CNS stem cells, which therefore are of considerable medical importance. First, aberrant behaviour of CNS stem cells is implicated in CNS tumors and CNS malformations. Second, CNS stem cells can be used in transplantation in neurodegenerative diseases, as a therapeutic approach. Third, new insights into neuronal differentiation of CNS stem cells may be important to improve treatment following injuries to the brain and spinal cord, in particular since it has recently been shown that also the adult CNS contains small populations of CNS stem cells.
This brings the CNS stem cell at the focus from a medical perspective and in this proposal we will address a number of key issues of CNS stem cell biology. We will do this in a series of 4 tasks with the participation of 5 different research groups in 5 countries, one of whom is an industrial partner. In task 1, we will compare the molecular characteristics of embryonic and adult CNS stem cells from three different CNS regions. This will lead to a better understanding of the cellular complexity and a more reliable identification of CNS stem cells. In task 2, we will analyse the function of individual genes in the Notch/Hes/Mash/Ngn signaling pathway, which is one of the major signaling systems controlling CNS stem cell development. This will be accomplished by ectopically expressing or functionally inactivating the genes in transgenic mice, which will link specific genetic alterations to particular effects on CNS development in vivo. In task 3, we will establish strategies allowing us to control proliferation and differentiation of CNS stem cells grown in culture. To this end, we will use antisense RNA and virus-based vectors to manipulate expression levels of Notch/Hes/Mash/Ngn genes. If successful, this would represent a major breakthrough in the domestication of these cells and be very important for the future use of cells in various forms of therapies. In task 4, we will identify novel genes specifically expressed under various stages of CNS stem cell maturation. This will enable us to establish a molecular "fingerprint" for different CNS stem cell populations, and in this way further improve the molecular characterization of these cells.
Collectively, findings from the 4 different tasks will be of considerable importance to cellular therapy, and to gain new insights into how differentiation of CNS stem cells can be experimentally controlled. Development of our research program and its exploitation represent an important opportunity for the European Research Community to contribute to health and future wealth creation in the European Union, as well as to a rapidly expanding research field in biomedicine and biotechnology.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesneurobiology
- natural sciencesbiological sciencescell biology
- medical and health sciencesmedical biotechnologycells technologiesstem cells
- natural sciencesbiological sciencesgeneticsRNA
- medical and health sciencesclinical medicinetransplantation
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Call for proposal
Data not availableFunding Scheme
CSC - Cost-sharing contractsCoordinator
171 77 STOCKHOLM
Sweden