Regenerative medicine uses stem cells to replace damaged tissues, but this approach requires therapeutic cells with known activity. There is currently no method to generate such cells in large quantities. In developing tissues, cell differentiation involves the appearance of growth factors at certain times to orchestrate differentiation. This project proposes to evaluate the use of viruses to activate genes in order to replicate that orchestration. Educational activities and lab tours will be designed to engage undergraduate and graduate students. A ‘‘Stem Cell and Art’’ showcase will highlight artistic, technical and ethical aspects of stem cell research. It will be developed for K-12 students, their families, and the general public.
In this project, human induced pluripotent stem cell (iPSC) differentiation will be enhanced. Genes specific to cell lineages will be manipulated epigenetically using dCas9 activators. A Synergistic Activation Mediator (SAM) system will be used to achieve target gene activation in iPSCs. Non-integrating Adeno-associated virus 1 (AAV1) will deliver SAM activators to iPSCs. Genome-scale activation screens to identify novel genes that facilitate endothelial progenitor (EP) differentiation will also be performed. The positive candidates will be used to enhance EP differentiation with AAV1-SAM. The investigators will also use AAV-SAM to promote beta cell differentiation. These results may provide compelling evidence that targeted gene activation using SAM could be employed to enhance iPSC differentiation. This would introduce a novel technology (SAM activators) to the stem cell differentiation toolkit in addition to small molecules and growth factors.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
