Single cell analysis of iPS derived neural stem cells and neurons

Abstract: In vitro derived neural stem cells can be used to model events of neurogenesis and neurodevelopmental dysfunction. Formation of stable neural stem cell environments relies on cellular components to stabilize cell-to-cell connections. Cell-to-cell connections are required to stabilize cell-to-cell communication and cell-signaling events that are required to maintain cell identity and cell integrity. Identifying gene expression profiles and protein expression profiles aid in discovery of cellular events governing functional neurogenesis and events leading to neurodevelopmental dysfunction. In Paper 1, we used single cell RNA-seq and identified cell adhesion molecule neurexin-1 alpha (NRXN1-α) as important for establishing functional efficient neural stem cells and for establishing functional neurons. In Paper 2, we used single cell RNA-seq and identified presence of inherent neurogenic progenitors and gliogenic progenitors in functional efficient neural stem cells and the neuronal or glial differentiation outcome to be linked to presence of predetermined progenitor cell types. In Paper 3, we identified microtubule stabilizing molecule doublecortin (DCX) as important for neuronal dendrite elongation, neuronal differentiation, and neuronal migration. In summary, this thesis demonstrates the potential of modeling neurodevelopment by using neural stem cells as a tool for investigation.