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Please use this identifier to cite or link to this item: http://hdl.handle.net/1807/25435

Title: Wnt Signaling in Human Neural Stem Cells and Brain Tumour Stem Cells
Authors: Brandon, Caroline
Advisor: Dirks, Peter Benjamin
Department: Laboratory Medicine and Pathobiology
Keywords: Wnt Signaling
Neural Stem Cells
Cancer Stem Cells
Brain Tumour
Issue Date: 15-Dec-2010
Abstract: We sought to determine whether activation of the Wnt signaling pathway altered the function of hNSCs in vitro. We took three approaches to activate Wnt signaling: Wnt3a, constitutively stabilized β-catenin (ΔN90), and the GSK3 inhibitor BIO. While Wnt3a and ΔN90 had no effect on proliferation in both stem cell (+EGF/FGF) and differentiating (-EGF/FGF) conditions, BIO reduced proliferation in both. All methods of Wnt signaling activation promoted neuronal lineage commitment during hNSC differentiation. Furthermore, BIO was able to induce mild neuronal differentiation in stem cell conditions, suggesting that GSK3-inhibition interferes with several pathways to regulate hNSC fate decisions. We also probed BTSC function using BIO-mediated GSK3 inhibition. We found that in stem cell conditions, BIO was able to induce neuronal differentiation, decrease proliferation, and induce cell cycle arrest. Together this data suggests that GSK3-inhibition, possibly through activation of Wnt signaling, may offer a novel mechanism for the differentiation treatment of glioblastomas.
URI: http://hdl.handle.net/1807/25435
Appears in Collections:Master
Department of Laboratory Medicine and Pathobiology - Master theses

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