Nitric oxide-induced DNA recombination & glycosaminoglycan mediated differentiation in stem cells

(cont.) Such therapeutic approaches require an understanding of the mechanisms regulating stem cell differentiation. The second part of this thesis investigates the role of HSGAGs in embryonic stem cell differentiation into endothelial cells. Differentiation of stem cells was accompanied by increases in the transcript levels of key HSGAG-biosynthetic enzymes, and the quantity of cell surface HSGAGs. Differentiation into endothelial cells was inhibited by ablation of the HSGAG-biosynthetic machinery by chlorate treatment, or by the enzymatic degradation of the HSGAGs. Exogenous addition of heparin to chlorate-treated cells partially restored differentiation into endothelial cells. These effects were mirrored in phospho-ERK levels, suggesting the involvement of the MAPK pathway. These results suggest that stem cell differentiation can be regulated by modulating the HSGAG moiety and this opens up new treatment modalities for cancer therapy and regenerative medicine.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Chemistry.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2005

Author dc:creator

• Kiziltepe, Tanyel, 1976-

Advisor dc:contributor.advisor

• Bevin P. Engelward and Ram Sasisekharan.

• Chemistry.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/30204

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/30204