{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/90492"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/90492","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Engineered microenvironments for studying liver progenitor differentiation","abstract":"The bipotential differentiation of liver progenitor cells underlies liver development and bile duct formation as well as liver regeneration and disease. Both TGFβ and Notch signaling are known to play important roles in the liver progenitor specification process and subsequent tissue morphogenesis. However, the complexity of these signaling pathways and their currently undefined interactions with other microenvironmental factors, including extracellular matrix (ECM), remain barriers to complete mechanistic understanding. Utilizing a series of strategies, including co-cultures and cellular microarrays, we identified distinct contributions of different Notch ligands and ECM proteins in the fate decisions of bipotential mouse embryonic liver (BMEL) progenitor cells. In particular, we demonstrated a cooperative influence of Jagged-1 and TGFβ1 on cholangiocytic differentiation. We established ECM-specific effects using cellular microarrays consisting of 32 distinct combinations of collagen I, collagen III, collagen IV, fibronectin, and laminin. In addition, we demonstrated that exogenous Jagged-1, Delta-like 1, and Delta-like 4 within the cellular microarray format was sufficient to induce cholangiocytic differentiation. Further, by combining Notch ligand microarrays with shRNA-based knockdown of Notch ligands, we systematically examined the effects of both cell-extrinsic and cell-intrinsic ligand. Our results highlight the importance of divergent Notch ligand function and combinatorial microenvironmental regulation in liver progenitor fate specification.","abstract_html":"The bipotential differentiation of liver progenitor cells underlies liver development and bile duct formation as well as liver regeneration and disease. Both TGFβ and Notch signaling are known to play important roles in the liver progenitor specification process and subsequent tissue morphogenesis. However, the complexity of these signaling pathways and their currently undefined interactions with other microenvironmental factors, including extracellular matrix (ECM), remain barriers to complete mechanistic understanding. Utilizing a series of strategies, including co-cultures and cellular microarrays, we identified distinct contributions of different Notch ligands and ECM proteins in the fate decisions of bipotential mouse embryonic liver (BMEL) progenitor cells. In particular, we demonstrated a cooperative influence of Jagged-1 and TGFβ1 on cholangiocytic differentiation. We established ECM-specific effects using cellular microarrays consisting of 32 distinct combinations of collagen I, collagen III, collagen IV, fibronectin, and laminin. In addition, we demonstrated that exogenous Jagged-1, Delta-like 1, and Delta-like 4 within the cellular microarray format was sufficient to induce cholangiocytic differentiation. Further, by combining Notch ligand microarrays with shRNA-based knockdown of Notch ligands, we systematically examined the effects of both cell-extrinsic and cell-intrinsic ligand. Our results highlight the importance of divergent Notch ligand function and combinatorial microenvironmental regulation in liver progenitor fate specification.","abstract_has_math":false,"creators":["Kaylan, Kerim Berk"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Bioengineering","degree_department":null,"school":null,"contributors":["Underhill, Gregory H."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-07-07T19:53:11Z","date_published":"2016-07-07T19:53:11Z","updated_at":"2026-07-22T22:26:32Z","subjects":["liver progenitors","bipotential liver progenitors","hepatoblasts","hepatocytes","cholangiocytes","bile duct cells","liver progenitor differentiation","osteopontin","Opn","Spp1","albumin","Alb","morphogenesis","tissue morphogenesis","bile duct morphogenesis","bile duct formation","liver development","Notch","Notch signaling","Jagged-1","Jag1","Delta-like 1","Dll1","Delta-like 4","Dll4","transforming growth factor β","TGFβ","TGFβ signaling","TGFβ1","Extracellular matrix proteins (ECM)","collagen I","collagen III","collagen IV","laminin","fibronectin","co-cultures","Green fluorescent protein (GFP)","microenvironment","microenvironmental regulation","cell microenvironment","cellular microenvironment","cell microarrays","cellular microarrays","engineered microenvironments"],"languages":["en"],"rights":["© 2016 Kerim B. 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Utilizing a series of strategies, including co-cultures and cellular microarrays, we identified distinct contributions of different Notch ligands and ECM proteins in the fate decisions of bipotential mouse embryonic liver (BMEL) progenitor cells. In particular, we demonstrated a cooperative influence of Jagged-1 and TGFβ1 on cholangiocytic differentiation. We established ECM-specific effects using cellular microarrays consisting of 32 distinct combinations of collagen I, collagen III, collagen IV, fibronectin, and laminin. In addition, we demonstrated that exogenous Jagged-1, Delta-like 1, and Delta-like 4 within the cellular microarray format was sufficient to induce cholangiocytic differentiation. Further, by combining Notch ligand microarrays with shRNA-based knockdown of Notch ligands, we systematically examined the effects of both cell-extrinsic and cell-intrinsic ligand. Our results highlight the importance of divergent Notch ligand function and combinatorial microenvironmental regulation in liver progenitor fate specification.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2016-07-07 without embargo terms","The student, Kerim Kaylan, accepted the attached license on 2016-03-28 at 12:35.","The student, Kerim Kaylan, submitted this Thesis for approval on 2016-03-28 at 12:45.","This Thesis was approved for publication on 2016-03-29 at 15:21.","DSpace SAF Submission Ingestion Package generated from Vireo submission #9123 on 2016-07-07 at 13:28:25","Made available in DSpace on 2016-07-07T19:53:11Z (GMT). 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However, the complexity of these signaling pathways and their currently undefined interactions with other microenvironmental factors, including extracellular matrix (ECM), remain barriers to complete mechanistic understanding. Utilizing a series of strategies, including co-cultures and cellular microarrays, we identified distinct contributions of different Notch ligands and ECM proteins in the fate decisions of bipotential mouse embryonic liver (BMEL) progenitor cells. In particular, we demonstrated a cooperative influence of Jagged-1 and TGFβ1 on cholangiocytic differentiation. We established ECM-specific effects using cellular microarrays consisting of 32 distinct combinations of collagen I, collagen III, collagen IV, fibronectin, and laminin. In addition, we demonstrated that exogenous Jagged-1, Delta-like 1, and Delta-like 4 within the cellular microarray format was sufficient to induce cholangiocytic differentiation. Further, by combining Notch ligand microarrays with shRNA-based knockdown of Notch ligands, we systematically examined the effects of both cell-extrinsic and cell-intrinsic ligand. Our results highlight the importance of divergent Notch ligand function and combinatorial microenvironmental regulation in liver progenitor fate specification.","Submission original under an indefinite embargo labeled 'Open Access'. The submission was exported from vireo on 2016-07-07 without embargo terms","The student, Kerim Kaylan, accepted the attached license on 2016-03-28 at 12:35.","The student, Kerim Kaylan, submitted this Thesis for approval on 2016-03-28 at 12:45.","This Thesis was approved for publication on 2016-03-29 at 15:21.","DSpace SAF Submission Ingestion Package generated from Vireo submission #9123 on 2016-07-07 at 13:28:25","Made available in DSpace on 2016-07-07T19:53:11Z (GMT). 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