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dc.titleA role for Chondroitin sulfate proteoglycan in regulating the survival and growth of neural stem cells
dc.contributor.authorANH VU MULY THAM
dc.identifier.citationANH VU MULY THAM (2009-08-21). A role for Chondroitin sulfate proteoglycan in regulating the survival and growth of neural stem cells. ScholarBank@NUS Repository.
dc.description.abstractNeural stem cells (NSCs) give rise to the nervous system during development, and persist in the adult to replace neurons in certain regions of the brain. NSCs can be isolated and maintained as neurospheres in vitro, and give rise to neurons, oligodendrocytes and astrocytes upon differentiation. Chondroitin sulfate proteoglycans (CSPGs) are components of the extracellular matrix and are involved in neural development. Here I show that CSPG is a component of the NSC-conditioned medium (NSC-CM), and is partly responsible for the ability of NSC-CM to stimulate neurosphere formation. Neurospheres can arise from NSCs or lineage restricted progenitors. To determine whether CSPG stimulates NSCs or progenitors, two cardinal features of stem cells were evaluated, self-renewal and multipotency. CSPG generated neurospheres can be expanded for at least seven times, and demonstrate increased proliferation in the neural colony forming cell assay (NCFCA). Clonally-derived neurospheres from CSPG treated cultures show increased multipotency. CSPG generated neurospheres display similar genetic profile as controls. The NSC frequency was estimated based on the percentage of clonally-derived neurospheres that displayed multipotency. CSPG increases the NSC frequency by more than three-fold. Thus CSPG stimulates NSC survival. CSPG also increases neurosphere size and reduces the population doubling time of neurospheres in culture, indicating that CSPG stimulates proliferation. In addition, CSPG is involved in maintaining the 3-dimensional structure of neurospheres. Using chondroitinase-ABC, sodium chlorate, ¿-D-xyloside and differentially sulfated chondroitin sulfate glycosaminoglycans (CS-GAGs), I dissected the structure of CSPG and attribute the regulation of NSC survival and proliferation to the full proteoglycan structure including specific sulfation motifs, whereas maintenance of the neurosphere structure requires only the CS-GAG. Lastly, I demonstrate that CSPG functions in NSC survival and proliferation via EGFR, JAK/STAT3 and PI3K signalling pathways.
dc.subjectchondroitin sulfate proteoglycan, neural stem cell, neurosphere, survival, signaling, conditioned medium
dc.contributor.supervisorSOHAIL AHMED
dc.contributor.supervisorDAWE, GAVIN STEWART
dc.description.degreeconferredDOCTOR OF PHILOSOPHY
Appears in Collections:Ph.D Theses (Open)

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