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Title: Derivation, maintenance and neuronal differentiation of mouse embryonic stem cells
Author: Chatzi, Christina
ISNI:       0000 0001 3530 4811
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 2008
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This thesis describes successful derivation of 10 novel ES cell lines from C57BL/6J blastocysts. They grow in colonies, express four stem cell markers, display normal karyotype, are able to differentiate in vitro and form chimeras in vivo.  Confirmation of germline transmission will enable them to be used for the production of novel mutants on pure C57BL/6J genetic background without backcrossing.  The maintenance of stemness of ES cells depends on delicate signalling networks.  Spontaneous differentiation is common in ES cell propagation, while its causing factors are largely unknown.  The data in this thesis show that ßDC, a dominant negative form of the retinoic acid receptor beta 2, regulates RA-mediated ES cell growth and differentiation.  ES cells expressing ßDC are resistant to 100nM RA-induced differentiation in monolayer, while upon 1mM RA induction during aggregation, they differentiate into mesodermal derivatives instead of ectodermal cells.  Remarkably, their capacity to participate in normal embryogenesis is not altered by ßDC expression and RA selection.  These findings raise the possibility that such a mutant may facilitate long-term maintenance of ES cells.  Defective GABAergic signalling is implicated in neurodevelopmental disorders, and brain/spinal cord injuries.  As a part of this thesis, a simple differentiation protocol has been developed, which leads to the production of a homogeneous population (93~96%) of GABAergic progenitors from mouse ES cells.  Translation of the above technologies to human ES cells may advance the stem cell replacement therapy.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available