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NSPCs are multipotent and give rise to the three main cell types in the brain: astrocytes, neurons, and oligodendrocytes. These cells come together to form the complex circuits and structures that make us who we are. Previous work in the Flanagan lab found that the sugar GlcNAc affects the fate of neural stem cells. How GlcNAc regulates NSPC fate remains unknown. However, recent work has shown that GlcNAc treatment appears to promote nuclear localization of Yap, indicating that Yap might be involved in how GlcNAc affects NSPCs fate bias. To assess our research question, we knocked down Yap in mouse NSPCs using siRNA. Immunocytochemistry was then used to identify our cells of interest by staining for known markers of mature neurons. Using fluorescence microscopy we were able to visualize and magnify our stained cells. After completing neuron quantifications, we found no clear effect of Yap siRNA treatment on neurogenesis with or without GlcNAc treatment. We noted interesting neuronal morphologies in Yap siRNA and GlcNAc-treated samples. Regenerative stem cell therapies offer promise as they can be applied to ameliorate deficiencies caused by traumatic brain injury, stroke or neurodegeneration. However, current Neural Stem and Progenitor Cells or NSPCs transplantation therapies would be more efficacious if they were optimized to allow for controlled fate bias of transplanted NSPCs, as different diseases require different compositions of the transplanted NSPC pools. Throughout this project, I explored whether the transcriptional protein Yap is involved in how the sugar GlcNAc affects NSPCs fate bias. Results from this project will contribute significantly to our understanding of NSPC differentiation and brain development and may yield novel targets for improving NSPC transplantation therapies.

Publication Date

4-1-2025

Keywords

neural stem and progenitor cells, NSPCs, GlcNAc, Yap protein, neurogenesis, cell fate bias, stem cell therapy, siRNA, immunocytochemistry, fluorescence microscopy, brain development, astrocytes, neurons, oligodendrocytes, regenerative medicine, neurodegeneration, traumatic brain injury, stroke, transcriptional regulation

Examining the Involvement of Yap in N-Glycan Branching Mediated NSPC Fate Bias

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