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Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation

Various subtypes of enteroendocrine cells (EECs) are present in the gut epithelium. EECs and pancreatic β-cells share similar pathways of differentiation during embryonic development and after birth. In this study, similarities between EECs and β-cells were evaluated in detail. To obtain specific su...

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Autores principales: Ryu, Gyeong Ryul, Lee, Esder, Kim, Jong Jin, Moon, Sung-Dae, Ko, Seung-Hyun, Ahn, Yu-Bae, Song, Ki-Ho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209304/
https://www.ncbi.nlm.nih.gov/pubmed/30379923
http://dx.doi.org/10.1371/journal.pone.0206401
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author Ryu, Gyeong Ryul
Lee, Esder
Kim, Jong Jin
Moon, Sung-Dae
Ko, Seung-Hyun
Ahn, Yu-Bae
Song, Ki-Ho
author_facet Ryu, Gyeong Ryul
Lee, Esder
Kim, Jong Jin
Moon, Sung-Dae
Ko, Seung-Hyun
Ahn, Yu-Bae
Song, Ki-Ho
author_sort Ryu, Gyeong Ryul
collection PubMed
description Various subtypes of enteroendocrine cells (EECs) are present in the gut epithelium. EECs and pancreatic β-cells share similar pathways of differentiation during embryonic development and after birth. In this study, similarities between EECs and β-cells were evaluated in detail. To obtain specific subtypes of EECs, cell sorting by flow cytometry was conducted from STC-1 cells (a heterogenous EEC line), and each single cell was cultured and passaged. Five EEC subtypes were established according to hormone expression, measured by quantitative RT-PCR and immunostaining: L, K, I, G and S cells expressing glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, cholecystokinin, gastrin and secretin, respectively. Each EEC subtype was found to express not only the corresponding gut hormone but also other gut hormones. Global microarray gene expression profiles revealed a higher similarity between each EEC subtype and MIN6 cells (a β-cell line) than between C2C12 cells (a myoblast cell line) and MIN6 cells, and all EEC subtypes were highly similar to each other. Genes for insulin secretion-related proteins were mostly enriched in EECs. However, gene expression of transcription factors crucial in mature β-cells, such as PDX1, MAFA and NKX6.1, were remarkably low in all EEC subtypes. Each EEC subtype showed variable methylation in three cytosine-guanosine dinucleotide sites in the insulin gene (Ins2) promoter, which were fully unmethylated in MIN6 cells. In conclusion, our data confirm that five EEC subtypes are closely related to β-cells, suggesting a potential target for cell-based therapy in type 1 diabetes.
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spelling pubmed-62093042018-11-19 Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation Ryu, Gyeong Ryul Lee, Esder Kim, Jong Jin Moon, Sung-Dae Ko, Seung-Hyun Ahn, Yu-Bae Song, Ki-Ho PLoS One Research Article Various subtypes of enteroendocrine cells (EECs) are present in the gut epithelium. EECs and pancreatic β-cells share similar pathways of differentiation during embryonic development and after birth. In this study, similarities between EECs and β-cells were evaluated in detail. To obtain specific subtypes of EECs, cell sorting by flow cytometry was conducted from STC-1 cells (a heterogenous EEC line), and each single cell was cultured and passaged. Five EEC subtypes were established according to hormone expression, measured by quantitative RT-PCR and immunostaining: L, K, I, G and S cells expressing glucagon-like peptide-1, glucose-dependent insulinotropic polypeptide, cholecystokinin, gastrin and secretin, respectively. Each EEC subtype was found to express not only the corresponding gut hormone but also other gut hormones. Global microarray gene expression profiles revealed a higher similarity between each EEC subtype and MIN6 cells (a β-cell line) than between C2C12 cells (a myoblast cell line) and MIN6 cells, and all EEC subtypes were highly similar to each other. Genes for insulin secretion-related proteins were mostly enriched in EECs. However, gene expression of transcription factors crucial in mature β-cells, such as PDX1, MAFA and NKX6.1, were remarkably low in all EEC subtypes. Each EEC subtype showed variable methylation in three cytosine-guanosine dinucleotide sites in the insulin gene (Ins2) promoter, which were fully unmethylated in MIN6 cells. In conclusion, our data confirm that five EEC subtypes are closely related to β-cells, suggesting a potential target for cell-based therapy in type 1 diabetes. Public Library of Science 2018-10-31 /pmc/articles/PMC6209304/ /pubmed/30379923 http://dx.doi.org/10.1371/journal.pone.0206401 Text en © 2018 Ryu et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Ryu, Gyeong Ryul
Lee, Esder
Kim, Jong Jin
Moon, Sung-Dae
Ko, Seung-Hyun
Ahn, Yu-Bae
Song, Ki-Ho
Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation
title Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation
title_full Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation
title_fullStr Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation
title_full_unstemmed Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation
title_short Comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation
title_sort comparison of enteroendocrine cells and pancreatic β-cells using gene expression profiling and insulin gene methylation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6209304/
https://www.ncbi.nlm.nih.gov/pubmed/30379923
http://dx.doi.org/10.1371/journal.pone.0206401
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