Date of Award
Honors College Thesis
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.
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Ortolano, Natalya A., "Activation of NF-κB Transcription Factor During In Vitro Differentiation of Mouse Embryonic Stem Cells" (2015). Honors Theses. 296.