Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.

The islets of Langerhans are critical endocrine micro-organs that secrete hormones regulating energy metabolism in animals. Insulin and glucagon, secreted by beta and alpha cells, respectively, are responsible for metabolic switching between fat and glucose utilization. Dysfunction in their secretio...

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Main Authors: Manu Aggarwal, Deborah A Striegel, Manami Hara, Vipul Periwal
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2023-11-01
Series:PLoS Computational Biology
Online Access:https://doi.org/10.1371/journal.pcbi.1011617
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author Manu Aggarwal
Deborah A Striegel
Manami Hara
Vipul Periwal
author_facet Manu Aggarwal
Deborah A Striegel
Manami Hara
Vipul Periwal
author_sort Manu Aggarwal
collection DOAJ
description The islets of Langerhans are critical endocrine micro-organs that secrete hormones regulating energy metabolism in animals. Insulin and glucagon, secreted by beta and alpha cells, respectively, are responsible for metabolic switching between fat and glucose utilization. Dysfunction in their secretion and/or counter-regulatory influence leads to diabetes. Debate in the field centers on the cytoarchitecture of islets, as the signaling that governs hormonal secretion depends on structural and functional factors, including electrical connectivity, innervation, vascularization, and physical proximity. Much effort has therefore been devoted to elucidating which architectural features are significant for function and how derangements in these features are correlated or causative for dysfunction, especially using quantitative network science or graph theory characterizations. Here, we ask if there are non-local features in islet cytoarchitecture, going beyond standard network statistics, that are relevant to islet function. An example is ring structures, or cycles, of α and δ cells surrounding β cell clusters or the opposite, β cells surrounding α and δ cells. These could appear in two-dimensional islet section images if a sphere consisting of one cell type surrounds a cluster of another cell type. To address these issues, we developed two independent computational approaches, geometric and topological, for such characterizations. For the latter, we introduce an application of topological data analysis to determine locations of topological features that are biologically significant. We show that both approaches, applied to a large collection of islet sections, are in complete agreement in the context both of developmental and diabetes-related changes in islet characteristics. The topological approach can be applied to three-dimensional imaging data for islets as well.
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spelling doaj-art-0bc03a2e37d74b8bba0b9fcb2130c8c32025-08-20T03:44:45ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582023-11-011911e101161710.1371/journal.pcbi.1011617Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.Manu AggarwalDeborah A StriegelManami HaraVipul PeriwalThe islets of Langerhans are critical endocrine micro-organs that secrete hormones regulating energy metabolism in animals. Insulin and glucagon, secreted by beta and alpha cells, respectively, are responsible for metabolic switching between fat and glucose utilization. Dysfunction in their secretion and/or counter-regulatory influence leads to diabetes. Debate in the field centers on the cytoarchitecture of islets, as the signaling that governs hormonal secretion depends on structural and functional factors, including electrical connectivity, innervation, vascularization, and physical proximity. Much effort has therefore been devoted to elucidating which architectural features are significant for function and how derangements in these features are correlated or causative for dysfunction, especially using quantitative network science or graph theory characterizations. Here, we ask if there are non-local features in islet cytoarchitecture, going beyond standard network statistics, that are relevant to islet function. An example is ring structures, or cycles, of α and δ cells surrounding β cell clusters or the opposite, β cells surrounding α and δ cells. These could appear in two-dimensional islet section images if a sphere consisting of one cell type surrounds a cluster of another cell type. To address these issues, we developed two independent computational approaches, geometric and topological, for such characterizations. For the latter, we introduce an application of topological data analysis to determine locations of topological features that are biologically significant. We show that both approaches, applied to a large collection of islet sections, are in complete agreement in the context both of developmental and diabetes-related changes in islet characteristics. The topological approach can be applied to three-dimensional imaging data for islets as well.https://doi.org/10.1371/journal.pcbi.1011617
spellingShingle Manu Aggarwal
Deborah A Striegel
Manami Hara
Vipul Periwal
Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.
PLoS Computational Biology
title Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.
title_full Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.
title_fullStr Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.
title_full_unstemmed Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.
title_short Geometric and topological characterization of the cytoarchitecture of islets of Langerhans.
title_sort geometric and topological characterization of the cytoarchitecture of islets of langerhans
url https://doi.org/10.1371/journal.pcbi.1011617
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AT deborahastriegel geometricandtopologicalcharacterizationofthecytoarchitectureofisletsoflangerhans
AT manamihara geometricandtopologicalcharacterizationofthecytoarchitectureofisletsoflangerhans
AT vipulperiwal geometricandtopologicalcharacterizationofthecytoarchitectureofisletsoflangerhans