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TITLE MEF2C-Directed Neurogenesis From Human Embryonic Stem Cells ABSTRACT Understanding differentiation of human embryonic stem cells (hESCs) provides insight into early human development and will help directing hESC differentiation for future cell-based therapies of Parkinsons disease, stroke and other neurodegenerative conditions. The PIs laboratory was the first to clone and characterize the transcription factor MEF2C, a protein that can direct the orchestra of genes to produce a particular type of cell, in this case a nerve cell (or neuron). We have demonstrated that MEF2C directs the differentiation of mouse ES cells into neurons and suppresses glial fate. MEF2C also helps keep new nerve cells alive, which is very helpful for their successful transplantation. However, little is known about the role of MEF2C in human neurogenesis, that is, its ability to direct hESC differentiation into neuronal lineages such as dopaminergic neurons to treat Parkinsons disease and its therapeutic potential to promote the generation of nerve cells in stem cell transplantation experiments. The goal of this application is to fill these gaps. The co-PIs laboratory has recently developed a unique procedure for the efficient differentiation of hESCs into a uniform population of neural precursor cells (NPCs), which are progenitor cells that develop from embryonic stem cells and can form different kinds of mature cells in the nervous system. Here, we will investigate if MEF2C can instruct hESC-derived NPCs to differentiate into nerve cells, including dopaminergic nerve cells for Parkinson
PI Stuart Lipton INSTITUTE Burnham Institute for Medical Research STATE California AMOUNT $3,036,000.00 AWARD DATE 2007 March GRANT TYPE Comprehensive