2026-09-22T16:12:28Z https://www.ideals.illinois.edu/oai-pmh

oai:www.ideals.illinois.edu:2142/116264 2023-07-11 col_2142_5131 col_2142_5163 com_2142_5130 com_2142_5162 com_2142_234

Underhill, Gregory H 2022-08 application/pdf en text Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2022-11-15 without embargo terms The student, Ishita Jain, accepted the attached license on 2022-07-18 at 13:00. The student, Ishita Jain, submitted this Thesis for approval on 2022-07-18 at 13:00. This Thesis was approved for publication on 2022-07-20 at 11:24. DSpace SAF Submission Ingestion Package generated from Vireo submission #18363 on 2022-11-15 at 18:21:25 Delineating cooperative effects of notch and biomechanical signals on patterned liver differentiation using modeling and cellular microarrays Jain, Ishita 2022-07-20 Patterned Liver Differentiation Notch Signaling Computational Modeling Controlled in vitro multicellular culture systems with defined biophysical microenvironment have been used to elucidate the role of Notch signaling in the spatiotemporal regulation of stem and progenitor cell differentiation. In addition, computational models incorporating features of Notch ligand-receptor interactions have provided important insights into Notch pathway signaling dynamics. However, the mechanistic relationship between Notch-mediated intercellular signaling and cooperative microenvironmental cues is less clear. Here, liver progenitor cell differentiation patterning was used as a model to systematically evaluate the complex interplay of cellular mechanics and Notch signaling along with identifying combinatorial mechanisms guiding progenitor fate. We present an integrated approach that pairs a computational intercellular signaling model with defined microscale culture configurations provided within a cell microarray platform. Specifically, the cell microarray-based experiments were used to validate and optimize parameters of the intercellular Notch signaling model. This model incorporated the experimentally established multicellular dimensions of the cellular microarray domains, mechanical stress-related activation parameters, and distinct Notch receptor-ligand interactions based on the roles of the Notch ligands Jagged-1 and Delta-like-1. Overall, these studies demonstrate the spatial control of mechanotransduction-associated components, key growth factor and Notch signaling interactions, and point towards a possible role of E-Cadherin in translating intercellular mechanical gradients to downstream Notch signaling. Thesis eng https://hdl.handle.net/2142/116264 Copyright 2022 Ishita Jain Thesis Bioengineering University of Illinois at Urbana-Champaign Bioengineering M.S.