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Title: Epigenetic features of neural differentiation and commitment
Author: Dvorkina, Maria
ISNI:       0000 0001 3436 4425
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2008
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Embryonic stem (ES) cells can be derived from preimplantation-stage embryos. Their ability to self-renew and give rise to the different cell types of the adult organism makes them a promising source of graft material for transplantation therapy. ES-cell differentiation is characterised by a loss of pluripotency and changes in gene expression and epigenetic status. Efficient protocols have been established to induce neural commitment of ES cells in vitro although the stability and long-term properties of transplanted ES-derived cells have not been fully explored. Here, I compared the epigenetic properties and lineage potential of mouse ES-derived neural progenitors with normal neural progenitors isolated from mouse embryonic brain. I show that both neural populations have similar epigenetic characteristics, such as replication timing and patterns of covalent histone modifications at the promoter regions of neural and non-neural genes. In particular, ex vivo and ES-derived neural progenitors both retain an 'opposing' or 'bivalent' pattern of histone modifications at some non-expressed developmental genes similar to that previously reported in ES cells. Bivalent chromatin was, however, resolved at these loci in self-renewing neural stem cells that are derived from ES . cells through the neural progenitor stage. These results suggest that bivalency is reduced as pluripotency is replaced by lineage restriction and that non-neural genes are subject to stable silencing upon neural differentiation. Reprogramming assays confirmed that ES-derived and ex vivo neural progenitors are more efficient donors for nuclear transfer than differentiated cells, such as lymphocytes, but less efficient than ES cells. Taken together, these findings suggest that changes in chromatin profile and epigenetic plasticity occur as ES commit to neural fate and that these changes are similar to those taking place in vivo during brain development.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available