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Title: Integrins and neural stem cells
Author: Hall, P. E.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2007
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Extracellular matrix (ECM)-rich basal laminae are an important component of other stem cell niches and thus are likely to form part of the NSC niche. Interactions with the ECM are mediated manly by cell surface heterodimers called integrins. β1 integrins have been implicated in maintaining human epidermal stem cells, and their elevated expression has allowed the enrichment of human prostate epithelial stem cells from transit amplifying populations. My work has focused on the role of the ECM and its receptors in the mammalian CNS stem cell niche. Initial experiments examined the conditions necessary to grow human NSCs under clonal conditions, before using these findings to demonstrate that these cells express higher levels of integrin α6β1 then progenitor or differential cell types. This led to the question of the role of integrins in NSC behaviour, which was investigated in vitro with human and murine tissue using integrin activating/blocking antibodies together with ECM molecules. Laminin-211, an α6β1 ligand, was found to increase NSC survival in an integrin-dependent manner. However, activation of integrin β1 did not recapitulate these results, indicating that integrin β1 is necessary, but not sufficient, for laminin to increase survival. Finally, in utero injections of the integrin activating/block antibodies into the lateral ventricle of embryonic day 15 (E15) embryos were conducted in order to examine the role of integrins in the in vivo stem cell niche. In conclusion, the findings indicate that integrins are highly expressed by neural stem cells and that integrins function in vitro and in vivo to influence stem cell behaviour.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available