THE EFFECTS OF SELECTED TRANSCRIPTION FACTORS AND SMALL MOLECULES ON CONVERTING GLIOBLASTOMA CELLS TO GABAERGIC NEURONS

Restricted (Penn State Only)
Author:
Hossain, Aasma
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Gong Chen, Thesis Supervisor
  • Michael Axtell, Honors Advisor
Keywords:
  • GABAergic neurons
  • Transcription factors
  • Glioblastoma
  • Cancer
  • Reprogramming efficiency
Abstract:
Previous studies have demonstrated that the overexpression of the transcription factor Ascl1 can reprogram human glioma cells to functional neurons both in vitro and in vivo. (Pedder et al., 2012; Suvà et al., 2014). In this study, a combination of six small molecules were added with the single transcription factors Ascl1 or NGN2 to convert cultured human glioblastoma cells to GABAergic neurons within 12 days with a conversion efficiency of 72% and 52%, respectively. Quantification of neuron markers DCX and MAP2 also reveals that the small molecules play a role in the overall increase of neuronal reprogramming efficiency. Interestingly, transcription factors alone can reduce the cell proliferation significantly, and addition of small molecules cannot further reduce the proliferation of glioma cells. The results indicate that both Ascl1 and NGN2 combined with the six small molecules, successfully converted glioma cells to neurons. However, NGN2 converted glioma cells into both glutamatergic and GABAergic neurons, whereas Ascl1 converted glioma cells significantly to GABAergic neurons. This study opens a new avenue to treating glioblastoma through less invasive approach when compared to conventional chemotherapy, and may have broad implications in cancer treatment in future trials.