Establishing a joint 2D/3D high throughput approach for evaluation of the effects of Wnt signaling and microenvironemtnal cues on liver progenitor cell differentiation
Grenci, Brock
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https://hdl.handle.net/2142/129202
Description
Title
Establishing a joint 2D/3D high throughput approach for evaluation of the effects of Wnt signaling and microenvironemtnal cues on liver progenitor cell differentiation
Author(s)
Grenci, Brock
Issue Date
2025-04-16
Director of Research (if dissertation) or Advisor (if thesis)
Underhill, Gregory H
Department of Study
Bioengineering
Discipline
Bioengineering
Degree Granting Institution
University of Illinois Urbana-Champaign
Degree Name
M.S.
Degree Level
Thesis
Keyword(s)
Liver Progenitor Cell
Wnt Signaling
Microenvironmental Cues
Language
eng
Abstract
Liver development is a complex process mediated by intrinsic cell genetics and the surrounding microenvironment. The Wnt/β-catenin pathway plays a crucial role in early liver development and homeostasis. Dysregulation of various parts of this pathway can cause disease, including many types of cancer. The mechanisms behind how these genetic alterations affect cell fate or spatial patterning in combination with microenvironmental cues is not fully understood, though. Here we demonstrate the effect of Wnt signaling alterations in combination with microenvironmental cues on liver progenitor cell fate and spatial patterning using well defined high throughput 2D and 3D culture platforms. Microcontact printing is used to create protein islands on polyacrylamide gels of varying stiffness, allowing for modulation of the 2D cellular microenvironment. Similarly, a high throughput PEG-acrylate microwell system is employed to study microenvironmental effects on liver progenitor cell differentiation in 3D. This is used in conjunction with shRNA mediated knockdowns to study combinatorial effects of intrinsic and extrinsic cellular factors on liver cell differentiation. We demonstrate that impairing the destruction complex increases biliary differentiation and decreases hepatic differentiation while also shifting spatial patterning of the cells. These changes in differentiation can be further tuned by the tissue microenvironment and show that recapitulating a diseased microenvironment can affect differentiation.
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