Date of Award

Spring 5-2021

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Biology

First Advisor

Jamie Newman

Abstract

Stem cells are unique in that they possess totipotent, pluripotent, or multipotent differentiation capabilities and can also self-renew. Stem cells are in either a state of selfrenewal or differentiation, but never both. If we are able to gain a full understanding of the underlying mechanisms that allow stem cells to remain self-renewing and multipotent, we will better be able to control the fate of cells, ultimately allowing stem cells to be used to their full capabilities in regenerative medicine. My research focuses on MED12 and its effects on Notch signaling. Here we describe the expression profile and activity of MED12, Notch1, and Notch3 in self-renewing human adipose stem cells and determine the impact that MED12 knockdown has on Notch1 and Notch3 expression and activity in self renewing hASC’s. We hypothesized that MED12 has a critical role in regulating transcription, while Notch signaling has a role in directing cell fate commitment. We observed that the knockdown of MED12 in hASCs has no effect on the protein expression of Notch1. We also observed that the knockdown of Notch3 does reduce the amount of MED12 transcript expressed in hASCs. To date, our data suggests that MED12 has no effect on Notch1 expression but does affect Notch3 expression. Also, the knockdown of Notch3 directly effects MED12 transcript. This data indicates a unique role for MED12 and a relationship with Notch3 in regulating cell state, leading us one step closer to realizing the clinical potential of these cells and using them in novel cell-based and tissue engineering therapies.

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