Date of Award
Honors College Thesis
Yanlin Guo, Ph.D.
Embryonic stem cells (ESCs) are a promising cell source for regenerative medicine. However, recent studies indicated that ESCs and ESC-derived cells (ESC-DCs) lack functional innate immunity against various pathogens and inflammatory cytokines. This presents a barrier to clinical application, as ESC-DCs would be placed in a wound site and exposed to pathogens and inflammatory cytokines. Using mouse ESCs (mESCs) as a model, we recently demonstrated that they are deficient in expressing type I interferons (IFN) and inflammatory cytokines. To determine the molecular basis for this finding, this study examined the activation state of nuclear factor-κB (NF-κB), a transcription factor that plays a key role in mediating the antiviral and inflammatory responses. Our results indicated that NF-κB in mESCs was not activated by TNFα, a cytokine that is known to induce strong inflammatory responses in differentiated cells. However, NF-κB was activated when mESCs were differentiated to fibroblasts (ESC-FBs). This was confirmed by NF-κB translocation from the cytoplasm to the nucleus upon TNFα treatment. Once in the nucleus, NF-κB activates transcription of immune related genes, but the expression of its regulated genes was much lower than in naturally differentiated FBs. Further analysis by RT-qPCR revealed that the expression of some NF-κB pathway components is upregulated in ESC-FBs. We conclude that the lack of innate immunity in mESCs is, at least partly, due to the inactivated status of NF-κB in mESCs.
Copyright for this thesis is owned by the author. It may be freely accessed by all users. However, any reuse or reproduction not covered by the exceptions of the Fair Use or Educational Use clauses of U.S. Copyright Law or without permission of the copyright holder may be a violation of federal law. Contact the administrator if you have additional questions.
Ortolano, Natalya A., "Activation of NF-κB Transcription Factor During In Vitro Differentiation of Mouse Embryonic Stem Cells" (2015). Honors Theses. 296.