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Effect of Medium Supplements on Mesenchymal Stromal Cell Development and Permissiveness to Transformation by EWSR1-FLI1 Fusion Protein

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Effect of Medium Supplements on Mesenchymal Stromal Cell Development and Permissiveness to Transformation by EWSR1-FLI1 Fusion Protein

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2020-01

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Ewing sarcoma is the second most frequent childhood bone tumor and is characterized by FET-ETS translocations. In ~ 85% of cases, the translocation fuses EWSR1 (a member of the FET gene family) with FLI1 (a member of the ETS family). Accurate models are required to study the mechanisms underlying tumorigenesis driven by EWSR1-FLI1, however no such models exist for Ewing sarcoma at present. The main obstacle to establishing a model for Ewing sarcoma is that the cell of origin remains undefined. A growing amount of evidence suggests that Ewing sarcoma originates from a small subset of mesenchymal stromal cells (MSC) permissive to the normally toxic EWSR1-FLI1 fusion protein. Characterizing this permissive subset is hindered by the substantial heterogeneity of MSCs. We sought to address this problem using induced pluripotent stem cells as a model system. It has been shown that some cytokines are capable of influencing the differentiation from iPSCs to MSCs, and the portion of different subpopulations of MSCs can be altered by changing the combination of cytokines that are involved in the differentiation. Herein, we characterized MSC derived from iPSC treated with different combinations of cytokines during differentiation with the ultimate goal of characterizing specific subsets of MSC that are permissive to EWSR1-FLI1.

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University of Minnesota M.S. thesis. January 2020. Major: Stem Cell Biology. Advisor: Beau Webber. 1 computer file (PDF); 38 pages.

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Lan, Tianxia. (2020). Effect of Medium Supplements on Mesenchymal Stromal Cell Development and Permissiveness to Transformation by EWSR1-FLI1 Fusion Protein. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/213041.

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