FPWR supported the creation of the first iPS cells from individuals with PWS, establishing a critical resource for the PWS research community. This valuable resource will will help researchers determine how PWS cells are different from typical cells, and will provide a platform to test small molecules, existing drugs, new drugs, genes, etc as potential therapies.
This team project was led by Marc Lalande at the Connecticut Stem Cell Institute. The team’s future goal is to use the cells to determine a list of genes that are specifically altered in PWS by next-generation RNA Sequencing of induced pluripotent stem cell-derived neurons.
From Dr. Marc LaLande: "In our laboratory, we have established induced pluripotent stem cell (iPSC) technology to create a model of Prader-Willi syndrome (PWS) in a test tube/tissue culture dish. To do this, we obtain skin cells from PWS and reprogram these into iPSCs that, like embryonic stem cells, have the capacity to become neurons. We plan to compare all the genes active in the neurons derived from the iPSCs of PWS to all the genes active in the neurons derived from iPSCs of normal individuals. To do this experiment, we are using the technique of next-generation sequencing. Our goal is to identify genes that have abnormal activity in PWS neurons. We will also search the results of the next-generation sequencing to discover genes that incorrectly put together in PWS i.e. genes that undergo abnormal splicing. From these experiments, we plan to produce a list of genes that are specifically altered in PWS and gain a better understanding of the underlying causes of PWS. Ultimately, we plan to establish a system whereby PWS neurons in tissue culture dishes can be used to screen for compounds that restore normal gene expression patterns and set the stage for the development of new therapeutic strategies