Defense Date

2011

Document Type

Thesis

Degree Name

Master of Science

Department

Human Genetics

First Advisor

Shawn Holt

Abstract

Induced Pluripotent Stem cells (iPScs) are artificially generated cells that demonstrate multilineage differentiation potential. These cells demonstrate similar morphology and high differentiation potential to Embryonic Stem Cells (ESCs). Generation of these cells from a terminally differentiated cell line requires activation of the core pluripotency genes Nanog, Oct4, and Sox2 as well as an oncogenic stimulus such as c-Myc. Here we examine the effect of the Human Pappiloma Virus derived proteins E6 and E7 on the ability of a terminally differentiated fibroblast cell line to a more primitive state and examine its multilineage differentiation capacity. In this paper, we attempt to differentiate BJ hTERT fibroblasts into adipogenic and osteogenic lineages with and without the core pluripotency factors Nanog, Oct4, Sox2 and also c-Myc using non-integrative adenoviral infections. We review the potential mechanisms through which changes in differentiation capacity changes occur through examination of the effects of E6 on the tumor suppressor protein p53. We determined that the proteins E6 and E7 when stably infected into BJ hTERT fibroblasts increase induced differentiation into adipogenic and osteogenic lineages. E6 and E7 can be considered components for generating cells with multipotent capacity with the addition of as little as one core pluripotency factor.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

August 2011

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