Intrinsic and extrinsic regulation of potency in the intestinal stem cell niche Public Deposited

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  • March 19, 2019
Creator
  • Gracz, Adam D.
    • Affiliation: School of Medicine, Department of Cell Biology and Physiology
Abstract
  • The intestinal epithelium is one of the most proliferative tissues in the adult body, undergoing near total renewal every 5-7 days. This remarkable turnover is driven by a small population of intestinal stem cells (ISCs), which maintain the physiological function and epithelial barrier integrity of the small intestine, and initiate repair following damage. While the anatomical location of ISCs has been appreciated for decades, the complex genetics and cellular behavior of these cells is still the subject of intense research and debate. Emerging research shows that patterns of ISC proliferation and differentiation are governed by highly complex interactions between the extrinsic signaling of the ISC niche and intrinsic genetic programs that regulate ISC behavior on the cell-autonomous level. In this dissertation, we aim to address the regulation of ISC potency at the intrinsic and extrinsic levels. We describe technologic approaches for the isolation and in vitro culture of two distinct human ISC populations, as well as advanced, high-throughput culture conditions for the study of ISC-niche interactions. To address ISC potency from the perspective of intrinsic genetic programming, we examine the role of Sry-box containing 4 (Sox4), which we demonstrate plays a role in ISC differentiation and proliferation, possibly through epigenetic mechanisms. Together, these studies provide valuable tools for examining the effects of extrinsic signaling on ISC potency in vitro, as well as describe a novel mechanistic regulator of ISC differentiation.
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  • In Copyright
Advisor
  • Magness, Scott
Degree
  • Doctor of Philosophy
Graduation year
  • 2013
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