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Extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from iPSCs

Induced pluripotent stem cells (iPSCs) have enormous potential in producing human tissues endlessly. We previously reported that type V collagen (COL5), a pancreatic extracellular matrix protein, promotes islet development and maturation from iPSCs. In this study, we identified a bioactive peptide d...

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Autores principales: Heaton, Emma S, Hu, Ming, Liu, Tianzheng, Hui, Huang, Tan, Yinfei, Ye, Kaiming, Jin, Sha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331343/
https://www.ncbi.nlm.nih.gov/pubmed/37435573
http://dx.doi.org/10.1177/20417314231185858
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author Heaton, Emma S
Hu, Ming
Liu, Tianzheng
Hui, Huang
Tan, Yinfei
Ye, Kaiming
Jin, Sha
author_facet Heaton, Emma S
Hu, Ming
Liu, Tianzheng
Hui, Huang
Tan, Yinfei
Ye, Kaiming
Jin, Sha
author_sort Heaton, Emma S
collection PubMed
description Induced pluripotent stem cells (iPSCs) have enormous potential in producing human tissues endlessly. We previously reported that type V collagen (COL5), a pancreatic extracellular matrix protein, promotes islet development and maturation from iPSCs. In this study, we identified a bioactive peptide domain of COL5, WWASKS, through bioinformatic analysis of decellularized pancreatic ECM (dpECM)-derived collagens. RNA-sequencing suggests that WWASKS induces the formation of pancreatic endocrine progenitors while suppressing the development of other types of organs. The expressions of hypoxic genes were significantly downregulated in the endocrine progenitors formed under peptide stimulation. Furthermore, we unveiled an enhancement of iPSC-derived islets’ (i-islets) glucose sensitivity under peptide stimulation. These i-islets secrete insulin in a glucose responsive manner. They were comprised of α, β, δ, and γ cells and were assembled into a tissue architecture similar to that of human islets. Mechanistically, the peptide is able to activate the canonical Wnt signaling pathway, permitting the translocation of β-catenin from the cytoplasm to the nucleus for pancreatic progenitor development. Collectively, for the first time, we demonstrated that an ECM-derived peptide dictates iPSC fate toward the generation of endocrine progenitors and subsequent islet organoids.
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spelling pubmed-103313432023-07-11 Extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from iPSCs Heaton, Emma S Hu, Ming Liu, Tianzheng Hui, Huang Tan, Yinfei Ye, Kaiming Jin, Sha J Tissue Eng Original Article Induced pluripotent stem cells (iPSCs) have enormous potential in producing human tissues endlessly. We previously reported that type V collagen (COL5), a pancreatic extracellular matrix protein, promotes islet development and maturation from iPSCs. In this study, we identified a bioactive peptide domain of COL5, WWASKS, through bioinformatic analysis of decellularized pancreatic ECM (dpECM)-derived collagens. RNA-sequencing suggests that WWASKS induces the formation of pancreatic endocrine progenitors while suppressing the development of other types of organs. The expressions of hypoxic genes were significantly downregulated in the endocrine progenitors formed under peptide stimulation. Furthermore, we unveiled an enhancement of iPSC-derived islets’ (i-islets) glucose sensitivity under peptide stimulation. These i-islets secrete insulin in a glucose responsive manner. They were comprised of α, β, δ, and γ cells and were assembled into a tissue architecture similar to that of human islets. Mechanistically, the peptide is able to activate the canonical Wnt signaling pathway, permitting the translocation of β-catenin from the cytoplasm to the nucleus for pancreatic progenitor development. Collectively, for the first time, we demonstrated that an ECM-derived peptide dictates iPSC fate toward the generation of endocrine progenitors and subsequent islet organoids. SAGE Publications 2023-07-08 /pmc/articles/PMC10331343/ /pubmed/37435573 http://dx.doi.org/10.1177/20417314231185858 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page (https://us.sagepub.com/en-us/nam/open-access-at-sage).
spellingShingle Original Article
Heaton, Emma S
Hu, Ming
Liu, Tianzheng
Hui, Huang
Tan, Yinfei
Ye, Kaiming
Jin, Sha
Extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from iPSCs
title Extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from iPSCs
title_full Extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from iPSCs
title_fullStr Extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from iPSCs
title_full_unstemmed Extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from iPSCs
title_short Extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from iPSCs
title_sort extracellular matrix-derived peptide stimulates the generation of endocrine progenitors and islet organoids from ipscs
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10331343/
https://www.ncbi.nlm.nih.gov/pubmed/37435573
http://dx.doi.org/10.1177/20417314231185858
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