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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...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482429/ https://www.ncbi.nlm.nih.gov/pubmed/37610090 http://dx.doi.org/10.7554/eLife.90006 |
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author | Tixi, Wilma Maldonado, Maricela Chang, Ya-Ting Chiu, Amy Yeung, Wilson Parveen, Nazia Nelson, Michael S Hart, Ryan Wang, Shihao Hsu, Wu Jih Fueger, Patrick Kopp, Janel L Huising, Mark O Dhawan, Sangeeta Shih, Hung Ping |
author_facet | Tixi, Wilma Maldonado, Maricela Chang, Ya-Ting Chiu, Amy Yeung, Wilson Parveen, Nazia Nelson, Michael S Hart, Ryan Wang, Shihao Hsu, Wu Jih Fueger, Patrick Kopp, Janel L Huising, Mark O Dhawan, Sangeeta Shih, Hung Ping |
author_sort | Tixi, Wilma |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-10482429 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-104824292023-09-07 Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation Tixi, Wilma Maldonado, Maricela Chang, Ya-Ting Chiu, Amy Yeung, Wilson Parveen, Nazia Nelson, Michael S Hart, Ryan Wang, Shihao Hsu, Wu Jih Fueger, Patrick Kopp, Janel L Huising, Mark O Dhawan, Sangeeta Shih, Hung Ping eLife Developmental Biology 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. eLife Sciences Publications, Ltd 2023-08-23 /pmc/articles/PMC10482429/ /pubmed/37610090 http://dx.doi.org/10.7554/eLife.90006 Text en © 2023, Tixi, Maldonado, Chang et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Developmental Biology Tixi, Wilma Maldonado, Maricela Chang, Ya-Ting Chiu, Amy Yeung, Wilson Parveen, Nazia Nelson, Michael S Hart, Ryan Wang, Shihao Hsu, Wu Jih Fueger, Patrick Kopp, Janel L Huising, Mark O Dhawan, Sangeeta Shih, Hung Ping Coordination between ECM and cell-cell adhesion regulates the development of islet aggregation, architecture, and functional maturation |
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 | Developmental Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482429/ https://www.ncbi.nlm.nih.gov/pubmed/37610090 http://dx.doi.org/10.7554/eLife.90006 |
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