This thesis shows that p53-deficient mouse glioma brain tumour stem cells (BTSCs), which fail to express pluripotency factors, can be reprogrammed with specific transcription factors to generate iPS cell lines (GNS-iPS) expressing endogenous pluripotency factors (Nanog, Oct4, and Rex1). GNS-iPS cell lines formed embryoid bodies (EBs) in vitro and undifferentiated growths in vivo that phenotypically did not resemble tumours derived from non-reprogrammed BTSCs. EBs formed from one GNS-iPS cell line expressed markers of mesoderm, endoderm, and ectoderm. Tumours produced from GNS-iPS cells had reduced astrocytic marker (GFAP) expression compared to those generated from control iPS cell lines or non-reprogrammed BTSCs. Preliminary results suggest that the reprogrammed cells can be re-differentiated into cells that show neural precursor phenotype. These findings suggest that BTSCs can acquire aspects of the pluripotent state with a defined set of transcription factors, opening the door for further exploration of reprogramming strategies to attenuate the cancer phenotype.
| Identifer | oai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/42904 |
| Date | 27 November 2013 |
| Creators | DiLabio, Julia Alexandra Maria |
| Contributors | Dirks, Peter Benjamin |
| Source Sets | University of Toronto |
| Language | en_ca |
| Detected Language | English |
| Type | Thesis |
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