Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation
Pancreatic islets are three-dimensional cell aggregates consisting of unique cellular composition, cell-to-cell contacts, and interactions with blood vessels. Cell aggregation is essential for islet endocrine function; however, it remains unclear how developing islets establish aggregation. By combi...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2023-08-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/90006 |
| _version_ | 1797691194051919872 |
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| author | Wilma Tixi Maricela Maldonado Ya-Ting Chang Amy Chiu Wilson Yeung Nazia Parveen Michael S Nelson Ryan Hart Shihao Wang Wu Jih Hsu Patrick Fueger Janel L Kopp Mark O Huising Sangeeta Dhawan Hung Ping Shih |
| author_facet | Wilma Tixi Maricela Maldonado Ya-Ting Chang Amy Chiu Wilson Yeung Nazia Parveen Michael S Nelson Ryan Hart Shihao Wang Wu Jih Hsu Patrick Fueger Janel L Kopp Mark O Huising Sangeeta Dhawan Hung Ping Shih |
| author_sort | Wilma Tixi |
| collection | DOAJ |
| description | Pancreatic islets are three-dimensional cell aggregates consisting of unique cellular composition, cell-to-cell contacts, and interactions with blood vessels. Cell aggregation is essential for islet endocrine function; however, it remains unclear how developing islets establish aggregation. By combining genetic animal models, imaging tools, and gene expression profiling, we demonstrate that islet aggregation is regulated by extracellular matrix signaling and cell-cell adhesion. Islet endocrine cell-specific inactivation of extracellular matrix receptor integrin β1 disrupted blood vessel interactions but promoted cell-cell adhesion and the formation of larger islets. In contrast, ablation of cell-cell adhesion molecule α-catenin promoted blood vessel interactions yet compromised islet clustering. Simultaneous removal of integrin β1 and α-catenin disrupts islet aggregation and the endocrine cell maturation process, demonstrating that establishment of islet aggregates is essential for functional maturation. Our study provides new insights into understanding the fundamental self-organizing mechanism for islet aggregation, architecture, and functional maturation. |
| first_indexed | 2024-03-12T02:10:50Z |
| format | Article |
| id | doaj.art-1af8a5ad4f5e48b9ad89b0e0e5e6d997 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-03-12T02:10:50Z |
| publishDate | 2023-08-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-1af8a5ad4f5e48b9ad89b0e0e5e6d9972023-09-06T13:26:45ZengeLife Sciences Publications LtdeLife2050-084X2023-08-011210.7554/eLife.90006Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturationWilma Tixi0Maricela Maldonado1https://orcid.org/0000-0003-4682-6900Ya-Ting Chang2Amy Chiu3Wilson Yeung4Nazia Parveen5Michael S Nelson6https://orcid.org/0000-0003-0480-5597Ryan Hart7Shihao Wang8Wu Jih Hsu9https://orcid.org/0000-0001-5385-9079Patrick Fueger10Janel L Kopp11https://orcid.org/0000-0002-1875-3401Mark O Huising12Sangeeta Dhawan13Hung Ping Shih14https://orcid.org/0000-0003-3035-5841Department of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United StatesDepartment of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United States; Department of Biomedical Engineering, College of Engineering, California State University, Long Beach, Long Beach, United StatesDepartment of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United StatesDepartment of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United StatesDepartment of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United StatesDepartment of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United StatesLight Microscopy Core, Beckman Research Institute, City of Hope, Duarte, United StatesDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United StatesDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, CanadaDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, CanadaDepartment of Molecular & Cellular Endocrinology, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United StatesDepartment of Cellular and Physiological Sciences, Life Sciences Institute, University of British Columbia, Vancouver, CanadaDepartment of Neurobiology, Physiology and Behavior, University of California, Davis, Davis, United States; Department of Physiology and Membrane Biology, School of Medicine, University of California, Davis, Davis, United StatesDepartment of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United StatesDepartment of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, Beckman Research Institute, City of Hope, Duarte, United StatesPancreatic islets are three-dimensional cell aggregates consisting of unique cellular composition, cell-to-cell contacts, and interactions with blood vessels. Cell aggregation is essential for islet endocrine function; however, it remains unclear how developing islets establish aggregation. By combining genetic animal models, imaging tools, and gene expression profiling, we demonstrate that islet aggregation is regulated by extracellular matrix signaling and cell-cell adhesion. Islet endocrine cell-specific inactivation of extracellular matrix receptor integrin β1 disrupted blood vessel interactions but promoted cell-cell adhesion and the formation of larger islets. In contrast, ablation of cell-cell adhesion molecule α-catenin promoted blood vessel interactions yet compromised islet clustering. Simultaneous removal of integrin β1 and α-catenin disrupts islet aggregation and the endocrine cell maturation process, demonstrating that establishment of islet aggregates is essential for functional maturation. Our study provides new insights into understanding the fundamental self-organizing mechanism for islet aggregation, architecture, and functional maturation.https://elifesciences.org/articles/90006ECMisletendocrine cellscell adhesionintegrinα-Catenin |
| spellingShingle | Wilma Tixi Maricela Maldonado Ya-Ting Chang Amy Chiu Wilson Yeung Nazia Parveen Michael S Nelson Ryan Hart Shihao Wang Wu Jih Hsu Patrick Fueger Janel L Kopp Mark O Huising Sangeeta Dhawan Hung Ping Shih Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation eLife ECM islet endocrine cells cell adhesion integrin α-Catenin |
| title | Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation |
| title_full | Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation |
| title_fullStr | Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation |
| title_full_unstemmed | Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation |
| title_short | Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation |
| title_sort | coordination between ecm and cell cell adhesion regulates the development of islet aggregation architecture and functional maturation |
| topic | ECM islet endocrine cells cell adhesion integrin α-Catenin |
| url | https://elifesciences.org/articles/90006 |
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