Using Small Molecules To Convert Human Astrocytes Into Functional Neurons

Open Access
Author:
Yeh, Hana
Area of Honors:
Biology
Degree:
Bachelor of Science
Document Type:
Thesis
Thesis Supervisors:
  • Gong Chen, Thesis Supervisor
  • Bernhard Luscher, Honors Advisor
Keywords:
  • gong chen
  • astrocytes
  • small molecules
  • conversion
Abstract:
Astrocytes are the most abundant cells in our central nervous system and play a critical role in neurodevelopment and the regulation of neuronal functions. Previous study in our lab has shown that overexpressing single transcription factor NeuroD1 can reprogram astrocytes into neurons both in vitro and in vivo. Here, we have found that small molecules are able to replace the transcription factor and successfully convert human astrocytes into functional neurons in vitro. These small molecules are known to be involved in normal developmental pathways such as Wnt and sonic hedgehog pathways. Based on immunocytochemistry and gene analysis, we were able to use a group of small molecules to inhibit astroglial phenotype and promote neuronal phenotype over two-week period. About 67% of the human astrocytes were successfully converted into neurons based on immunocytochemistry analysis. The converted neurons were fully functional and consisted of mainly glutamatergic neurons. This chemical reprogramming method may potentially be developed into drug therapy for brain repair and provide a new and less invasive approach in brain repair.