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postgraduate thesis: A study of membrane-bound neuregulin in mediating fate commitment of Schwann cell-like cells

TitleA study of membrane-bound neuregulin in mediating fate commitment of Schwann cell-like cells
Authors
Advisors
Issue Date2013
PublisherThe University of Hong Kong (Pokfulam, Hong Kong)
Citation
Leung, H. [梁可昕]. (2013). A study of membrane-bound neuregulin in mediating fate commitment of Schwann cell-like cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5108701
AbstractCentral nervous system injuries often lead to devastating consequences due to an unfavourable environment created after the injury. Current treatments have yet to address the environment for improved prospects of functional recovery. Transplantation of Schwann cells into the lesion site could in part address the issue, promoting nerve regeneration and enhancing functional recovery. Bone marrow stromal cells (BMSCs) promise to be a viable, autologous source for Schwann cell derivation. Fate-committed Schwann cells derived from BMSCs through co-culture with purified dorsal root ganglia (DRG) neurons suggest that the DRG neurons present juxtacrine cues that direct commitment to the Schwann cell fate. We hypothesize that Neuregulin 1 type III (NRG1(III)) is one such juxtacrine cue to which BMSC-derived Schwann cell-like cells (SCLC) respond in the switch to fate commitment. In this study, NRG1(III) was found to be expressed on freshly isolated DRG neurons and that SCLCs expressed both the ErbB2 and 3 receptors. Western blot analysis for phosphorylated Akt and MAPK provided indicators of downstream signalling of NRG1/ErbB complexes. We then tested if both the soluble and membrane bound forms of NRG1 mediate SCLC differentiation towards fate commitment. In contrast to the membrane-bound form on DRG neurons, soluble NRG1 failed to direct the SCLCs towards the Schwann cell fate. HEK293T cells that stably overexpress NRG1(III) were generated and tested as a neuronal surrogate that presents NRG1(III) on the cell surface. In a 5-day co-culture system with HEK293TNrg1(III) cells, SCLCs were found to develop elongated processes, acquiring either unipolar or bipolar morphology that resembles that of Schwann cells. Screening for marker expression by RT-PCR suggested that at this stage of morphological transition, SCLCs were not yet committed to the Schwann cell fate. The co-culture system will be pursued to find ex vivo conditions that direct differentiation of BMSC-derived SCLCs to fate-committed Schwann cells.
DegreeMaster of Philosophy
SubjectNeuroglia
Mesenchymal stem cells
Dept/ProgramBiochemistry
Persistent Identifierhttp://hdl.handle.net/10722/193482

 

DC FieldValueLanguage
dc.contributor.advisorChan, YS-
dc.contributor.advisorShum, DKY-
dc.contributor.authorLeung, Ho-yan-
dc.contributor.author梁可昕-
dc.date.accessioned2014-01-10T09:45:54Z-
dc.date.available2014-01-10T09:45:54Z-
dc.date.issued2013-
dc.identifier.citationLeung, H. [梁可昕]. (2013). A study of membrane-bound neuregulin in mediating fate commitment of Schwann cell-like cells. (Thesis). University of Hong Kong, Pokfulam, Hong Kong SAR. Retrieved from http://dx.doi.org/10.5353/th_b5108701-
dc.identifier.urihttp://hdl.handle.net/10722/193482-
dc.description.abstractCentral nervous system injuries often lead to devastating consequences due to an unfavourable environment created after the injury. Current treatments have yet to address the environment for improved prospects of functional recovery. Transplantation of Schwann cells into the lesion site could in part address the issue, promoting nerve regeneration and enhancing functional recovery. Bone marrow stromal cells (BMSCs) promise to be a viable, autologous source for Schwann cell derivation. Fate-committed Schwann cells derived from BMSCs through co-culture with purified dorsal root ganglia (DRG) neurons suggest that the DRG neurons present juxtacrine cues that direct commitment to the Schwann cell fate. We hypothesize that Neuregulin 1 type III (NRG1(III)) is one such juxtacrine cue to which BMSC-derived Schwann cell-like cells (SCLC) respond in the switch to fate commitment. In this study, NRG1(III) was found to be expressed on freshly isolated DRG neurons and that SCLCs expressed both the ErbB2 and 3 receptors. Western blot analysis for phosphorylated Akt and MAPK provided indicators of downstream signalling of NRG1/ErbB complexes. We then tested if both the soluble and membrane bound forms of NRG1 mediate SCLC differentiation towards fate commitment. In contrast to the membrane-bound form on DRG neurons, soluble NRG1 failed to direct the SCLCs towards the Schwann cell fate. HEK293T cells that stably overexpress NRG1(III) were generated and tested as a neuronal surrogate that presents NRG1(III) on the cell surface. In a 5-day co-culture system with HEK293TNrg1(III) cells, SCLCs were found to develop elongated processes, acquiring either unipolar or bipolar morphology that resembles that of Schwann cells. Screening for marker expression by RT-PCR suggested that at this stage of morphological transition, SCLCs were not yet committed to the Schwann cell fate. The co-culture system will be pursued to find ex vivo conditions that direct differentiation of BMSC-derived SCLCs to fate-committed Schwann cells.-
dc.languageeng-
dc.publisherThe University of Hong Kong (Pokfulam, Hong Kong)-
dc.relation.ispartofHKU Theses Online (HKUTO)-
dc.rightsThe author retains all proprietary rights, (such as patent rights) and the right to use in future works.-
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.lcshNeuroglia-
dc.subject.lcshMesenchymal stem cells-
dc.titleA study of membrane-bound neuregulin in mediating fate commitment of Schwann cell-like cells-
dc.typePG_Thesis-
dc.identifier.hkulb5108701-
dc.description.thesisnameMaster of Philosophy-
dc.description.thesislevelMaster-
dc.description.thesisdisciplineBiochemistry-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.5353/th_b5108701-
dc.date.hkucongregation2013-

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