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Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA
Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. Furthermore, our recent study demonstrated the generation of induced tissue-specific stem (iTS) cells by transient overexpression of the reprogrammi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098023/ https://www.ncbi.nlm.nih.gov/pubmed/30120295 http://dx.doi.org/10.1038/s41598-018-30784-0 |
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author | Miyagi-Shiohira, Chika Nakashima, Yoshiki Kobayashi, Naoya Saitoh, Issei Watanabe, Masami Noguchi, Hirofumi |
author_facet | Miyagi-Shiohira, Chika Nakashima, Yoshiki Kobayashi, Naoya Saitoh, Issei Watanabe, Masami Noguchi, Hirofumi |
author_sort | Miyagi-Shiohira, Chika |
collection | PubMed |
description | Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. Furthermore, our recent study demonstrated the generation of induced tissue-specific stem (iTS) cells by transient overexpression of the reprogramming factors using a plasmid combined with tissue-specific selection. In this study, we were able to generate RNA-based iTS cells that utilize a single, synthetic, self-replicating VEE-RF RNA replicon expressing four reprogramming factors (OCT4, KLF4, SOX2, and GLIS1). A single VEE-RF RNA transfection into mouse pancreatic tissue resulted in efficient generation of iTS cells from pancreas (iTS-P cells) with genetic markers of endoderm and pancreatic progenitors and differentiation into insulin-producing cells more efficiently than ES cells. Subcutaneous transplantation of iTS-P cells into immunodeficient mice resulted in no teratoma formation. Bisulfite genomic sequencing demonstrated that the promoters of Oct4 and Nanog remained partially methylated in iTS-P cells. We compared the global gene-expression profiles of ES cells, iTS-P cells, and pancreatic islets. Microarray analyses confirmed that the iTS-P cells were similar but not identical to ES cells compared with islets. These data suggest that iTS-P cells are cells that inherit numerous components of epigenetic memory from pancreas cells and acquire self-renewal potential. The generation of iTS cells may have important implications for the clinical application of stem cells. |
format | Online Article Text |
id | pubmed-6098023 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-60980232018-08-23 Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA Miyagi-Shiohira, Chika Nakashima, Yoshiki Kobayashi, Naoya Saitoh, Issei Watanabe, Masami Noguchi, Hirofumi Sci Rep Article Induced pluripotent stem (iPS) cells have significant implications for overcoming most of the ethical issues associated with embryonic stem (ES) cells. Furthermore, our recent study demonstrated the generation of induced tissue-specific stem (iTS) cells by transient overexpression of the reprogramming factors using a plasmid combined with tissue-specific selection. In this study, we were able to generate RNA-based iTS cells that utilize a single, synthetic, self-replicating VEE-RF RNA replicon expressing four reprogramming factors (OCT4, KLF4, SOX2, and GLIS1). A single VEE-RF RNA transfection into mouse pancreatic tissue resulted in efficient generation of iTS cells from pancreas (iTS-P cells) with genetic markers of endoderm and pancreatic progenitors and differentiation into insulin-producing cells more efficiently than ES cells. Subcutaneous transplantation of iTS-P cells into immunodeficient mice resulted in no teratoma formation. Bisulfite genomic sequencing demonstrated that the promoters of Oct4 and Nanog remained partially methylated in iTS-P cells. We compared the global gene-expression profiles of ES cells, iTS-P cells, and pancreatic islets. Microarray analyses confirmed that the iTS-P cells were similar but not identical to ES cells compared with islets. These data suggest that iTS-P cells are cells that inherit numerous components of epigenetic memory from pancreas cells and acquire self-renewal potential. The generation of iTS cells may have important implications for the clinical application of stem cells. Nature Publishing Group UK 2018-08-17 /pmc/articles/PMC6098023/ /pubmed/30120295 http://dx.doi.org/10.1038/s41598-018-30784-0 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Miyagi-Shiohira, Chika Nakashima, Yoshiki Kobayashi, Naoya Saitoh, Issei Watanabe, Masami Noguchi, Hirofumi Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA |
title | Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA |
title_full | Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA |
title_fullStr | Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA |
title_full_unstemmed | Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA |
title_short | Characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative RNA |
title_sort | characterization of induced tissue-specific stem cells from pancreas by a synthetic self-replicative rna |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6098023/ https://www.ncbi.nlm.nih.gov/pubmed/30120295 http://dx.doi.org/10.1038/s41598-018-30784-0 |
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