Angiopoietins stimulate pancreatic islet development from stem cells

Abstract In vitro differentiation of human induced pluripotent stem cells (iPSCs) into functional islets holds immense potential to create an unlimited source of islets for diabetes research and treatment. A continuous challenge in this field is to generate glucose-responsive mature islets. We herei...

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Autores principales:	Soujanya S. Karanth, Shuofei Sun, Huanjing Bi, Kaiming Ye, Sha Jin
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/72f5781725454200a86642b965d26d18
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spelling	oai:doaj.org-article:72f5781725454200a86642b965d26d182021-12-02T16:31:51ZAngiopoietins stimulate pancreatic islet development from stem cells10.1038/s41598-021-92922-52045-2322https://doaj.org/article/72f5781725454200a86642b965d26d182021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-92922-5https://doaj.org/toc/2045-2322Abstract In vitro differentiation of human induced pluripotent stem cells (iPSCs) into functional islets holds immense potential to create an unlimited source of islets for diabetes research and treatment. A continuous challenge in this field is to generate glucose-responsive mature islets. We herein report a previously undiscovered angiopoietin signal for in vitro islet development. We revealed, for the first time, that angiopoietins, including angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) permit the generation of islets from iPSCs with elevated glucose responsiveness, a hallmark of mature islets. Angiopoietin-stimulated islets exhibited glucose synchronized calcium ion influx in repetitive glucose challenges. Moreover, Ang2 augmented the expression of all islet hormones, including insulin, glucagon, somatostatin, and pancreatic polypeptide; and β cell transcription factors, including NKX6.1, MAFA, UCN3, and PDX1. Furthermore, we showed that the Ang2 stimulated islets were able to regulate insulin exocytosis through actin-filament polymerization and depolymerization upon glucose challenge, presumably through the CDC42-RAC1-gelsolin mediated insulin secretion signaling pathway. We also discovered the formation of endothelium within the islets under Ang2 stimulation. These results strongly suggest that angiopoietin acts as a signaling molecule to endorse in vitro islet development from iPSCs.Soujanya S. KaranthShuofei SunHuanjing BiKaiming YeSha JinNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Soujanya S. Karanth Shuofei Sun Huanjing Bi Kaiming Ye Sha Jin Angiopoietins stimulate pancreatic islet development from stem cells
description	Abstract In vitro differentiation of human induced pluripotent stem cells (iPSCs) into functional islets holds immense potential to create an unlimited source of islets for diabetes research and treatment. A continuous challenge in this field is to generate glucose-responsive mature islets. We herein report a previously undiscovered angiopoietin signal for in vitro islet development. We revealed, for the first time, that angiopoietins, including angiopoietin-1 (Ang1) and angiopoietin-2 (Ang2) permit the generation of islets from iPSCs with elevated glucose responsiveness, a hallmark of mature islets. Angiopoietin-stimulated islets exhibited glucose synchronized calcium ion influx in repetitive glucose challenges. Moreover, Ang2 augmented the expression of all islet hormones, including insulin, glucagon, somatostatin, and pancreatic polypeptide; and β cell transcription factors, including NKX6.1, MAFA, UCN3, and PDX1. Furthermore, we showed that the Ang2 stimulated islets were able to regulate insulin exocytosis through actin-filament polymerization and depolymerization upon glucose challenge, presumably through the CDC42-RAC1-gelsolin mediated insulin secretion signaling pathway. We also discovered the formation of endothelium within the islets under Ang2 stimulation. These results strongly suggest that angiopoietin acts as a signaling molecule to endorse in vitro islet development from iPSCs.
format	article
author	Soujanya S. Karanth Shuofei Sun Huanjing Bi Kaiming Ye Sha Jin
author_facet	Soujanya S. Karanth Shuofei Sun Huanjing Bi Kaiming Ye Sha Jin
author_sort	Soujanya S. Karanth
title	Angiopoietins stimulate pancreatic islet development from stem cells
title_short	Angiopoietins stimulate pancreatic islet development from stem cells
title_full	Angiopoietins stimulate pancreatic islet development from stem cells
title_fullStr	Angiopoietins stimulate pancreatic islet development from stem cells
title_full_unstemmed	Angiopoietins stimulate pancreatic islet development from stem cells
title_sort	angiopoietins stimulate pancreatic islet development from stem cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/72f5781725454200a86642b965d26d18
work_keys_str_mv	AT soujanyaskaranth angiopoietinsstimulatepancreaticisletdevelopmentfromstemcells AT shuofeisun angiopoietinsstimulatepancreaticisletdevelopmentfromstemcells AT huanjingbi angiopoietinsstimulatepancreaticisletdevelopmentfromstemcells AT kaimingye angiopoietinsstimulatepancreaticisletdevelopmentfromstemcells AT shajin angiopoietinsstimulatepancreaticisletdevelopmentfromstemcells
_version_	1718383815309656064

Angiopoietins stimulate pancreatic islet development from stem cells

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