Date of Award

Summer 8-2021

Document Type

Thesis

Degree Name

Master of Science (MS)

Department

Molecular Science and Nanotechnology

First Advisor

Jamie Newman

Abstract

Human adipose-derived stem cells (hASCs) have significant therapeutic potential due to their ability to self-renew, differentiate down multiple lineages, and modulate the immune system. In addition to these many benefits, hASCs boast a minimally invasive harvesting procedure, making them a readily available cell source for stem cell research and tissue regeneration (Ock, et al. 2016) (Abdi, et al. 2008). Despite their broad use, very little is known about the mechanisms that control cell fate.


One way to enhance our mechanistic understanding of differentiation is through the systematic examination of the signaling pathways. The Notch signaling pathway is a highly conserved, contact dependent, cell-to-cell signaling cascade known to regulate cell state and multipotent differentiation of hASCs. This pathway consists of four unique receptors and five unique ligands (Braune and Lendahl 2016). Two receptors believed to play a significant role in regulating osteogenic differentiation are Notch1 and Notch3.

Here the expression of Notch1 and Notch3 are characterized during osteogenesis and the effect that siRNA-mediated knockdown of each receptor has on osteogenic differentiation is evaluated. By studying changes in osteogenic marker expression following a reduction in Notch expression and activity, we will be able to determine how each receptor individually affects the osteogenic potential of hASCs and identify potential novel therapeutic targets to treat bone damage and loss.

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