Attenuated Responses To Inflammatory Cytokines In Mouse Embryonic Stem Cells: Biological Implications And The Molecular Basis

<p>Embryonic stem cells (ESCs) have attracted intense interest due to their great potential for regenerative medicine. However, their immune property is an overlooked but a significant issue that needs to be thoroughly investigated not only to resolve the concern for therapeutic applications but also for further understanding the early stage of organismal development. Recent studies demonstrated that ESCs are deficient in innate immune responses to viral/bacterial infections and inflammatory cytokines. Inflammatory conditions generally inhibit cell proliferation, which could be detrimental to ESCs, since cell proliferation is their dedicated task during early embryogenesis. Thus, I hypothesize that the attenuated innate immunity in ESCs could allow them to evade the cytotoxicity caused by immune reactions and is, therefore, a self-protective mechanism during early embryogenesis. We have differentiated mouse ESCs (mESCs) to fibroblast-like cells (mESC-FBs) which were proved to have partially developed innate immunity. Using these cells as a model for comparison with mESCs, the insensitivity of mESCs to the cytotoxic effects from IFNg, which is an inflammatory cytokine highly presented during early embryogenesis, and other inflammatory conditions were demonstrated, including attenuated expressions of inflammatory and signaling molecules, inactivated transcription factor and unaffected cell viability. Furthermore, basal expressions of protein phosphatases that inhibit IFNg pathway were higher in mESCs than mESC-FBs. Treating mESCs with protein phosphatases inhibitor upregulated the expression of IFNg induced signaling molecule. In all, the attenuated inflammatory responses are beneficial for mESCs, and the inhibition effects from protein phosphatases could, at least, partially explain their attenuated responses to IFNg.</p>

Name thesis:degree_name

Master of Science (MS)

Level thesis:degree_level

Masters Thesis

Year dc:date.available

2019

Author dc:creator

• Chen, Bohan

Contributors dc:contributor

• Yan-Lin Guo
• Alex Flynt
• Fengwei Bai

• Embryonic Stem Cells
• Innate Immunity
• Inflammatory Cytokine
• Cell Biology
• Developmental Biology
• Immunity

Repository record dc:identifier

https://aquila.usm.edu/masters_theses/650

OAI identifier oai:identifier

oai:aquila.usm.edu:masters_theses-1702