Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2023
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
_version_ 1785102171697577984
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
work_keys_str_mv AT tixiwilma coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT maldonadomaricela coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT changyating coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT chiuamy coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT yeungwilson coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT parveennazia coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT nelsonmichaels coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT hartryan coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT wangshihao coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT hsuwujih coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT fuegerpatrick coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT koppjanell coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT huisingmarko coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT dhawansangeeta coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation
AT shihhungping coordinationbetweenecmandcellcelladhesionregulatesthedevelopmentofisletaggregationarchitectureandfunctionalmaturation