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Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors

We recently demonstrated the generation of mouse induced tissue-specific stem (iTS) cells through transient overexpression of reprogramming factors combined with tissue-specific selection. Here we induced expandable tissue-specific progenitor (iTP) cells from human pancreatic tissue through transien...

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Autores principales: Noguchi, Hirofumi, Miyagi-Shiohira, Chika, Nakashima, Yoshiki, Kinjo, Takao, Kobayashi, Naoya, Saitoh, Issei, Watanabe, Masami, Shapiro, A. M. James, Kin, Tatsuya
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society of Gene & Cell Therapy 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383192/
https://www.ncbi.nlm.nih.gov/pubmed/30828587
http://dx.doi.org/10.1016/j.omtm.2019.01.011
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author Noguchi, Hirofumi
Miyagi-Shiohira, Chika
Nakashima, Yoshiki
Kinjo, Takao
Kobayashi, Naoya
Saitoh, Issei
Watanabe, Masami
Shapiro, A. M. James
Kin, Tatsuya
author_facet Noguchi, Hirofumi
Miyagi-Shiohira, Chika
Nakashima, Yoshiki
Kinjo, Takao
Kobayashi, Naoya
Saitoh, Issei
Watanabe, Masami
Shapiro, A. M. James
Kin, Tatsuya
author_sort Noguchi, Hirofumi
collection PubMed
description We recently demonstrated the generation of mouse induced tissue-specific stem (iTS) cells through transient overexpression of reprogramming factors combined with tissue-specific selection. Here we induced expandable tissue-specific progenitor (iTP) cells from human pancreatic tissue through transient expression of genes encoding the reprogramming factors OCT4 (octamer-binding transcription factor 4), p53 small hairpin RNA (shRNA), SOX2 (sex-determining region Y-box 2), KLF4 (Kruppel-like factor 4), L-MYC, and LIN28. Transfection of episomal plasmid vectors into human pancreatic tissue efficiently generated iTP cells expressing genetic markers of endoderm and pancreatic progenitors. The iTP cells differentiated into insulin-producing cells more efficiently than human induced pluripotent stem cells (iPSCs). iTP cells continued to proliferate faster than pancreatic tissue cells until days 100–120 (passages 15–20). iTP cells subcutaneously inoculated into immunodeficient mice did not form teratomas. Genomic bisulfite nucleotide sequence analysis demonstrated that the OCT4 and NANOG promoters remained partially methylated in iTP cells. We compared the global gene expression profiles of iPSCs, iTP cells, and pancreatic cells (islets >80%). Microarray analyses revealed that the gene expression profiles of iTP cells were similar, but not identical, to those of iPSCs but different from those of pancreatic cells. The generation of human iTP cells may have important implications for the clinical application of stem/progenitor cells.
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spelling pubmed-63831922019-03-01 Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors Noguchi, Hirofumi Miyagi-Shiohira, Chika Nakashima, Yoshiki Kinjo, Takao Kobayashi, Naoya Saitoh, Issei Watanabe, Masami Shapiro, A. M. James Kin, Tatsuya Mol Ther Methods Clin Dev Article We recently demonstrated the generation of mouse induced tissue-specific stem (iTS) cells through transient overexpression of reprogramming factors combined with tissue-specific selection. Here we induced expandable tissue-specific progenitor (iTP) cells from human pancreatic tissue through transient expression of genes encoding the reprogramming factors OCT4 (octamer-binding transcription factor 4), p53 small hairpin RNA (shRNA), SOX2 (sex-determining region Y-box 2), KLF4 (Kruppel-like factor 4), L-MYC, and LIN28. Transfection of episomal plasmid vectors into human pancreatic tissue efficiently generated iTP cells expressing genetic markers of endoderm and pancreatic progenitors. The iTP cells differentiated into insulin-producing cells more efficiently than human induced pluripotent stem cells (iPSCs). iTP cells continued to proliferate faster than pancreatic tissue cells until days 100–120 (passages 15–20). iTP cells subcutaneously inoculated into immunodeficient mice did not form teratomas. Genomic bisulfite nucleotide sequence analysis demonstrated that the OCT4 and NANOG promoters remained partially methylated in iTP cells. We compared the global gene expression profiles of iPSCs, iTP cells, and pancreatic cells (islets >80%). Microarray analyses revealed that the gene expression profiles of iTP cells were similar, but not identical, to those of iPSCs but different from those of pancreatic cells. The generation of human iTP cells may have important implications for the clinical application of stem/progenitor cells. American Society of Gene & Cell Therapy 2019-01-29 /pmc/articles/PMC6383192/ /pubmed/30828587 http://dx.doi.org/10.1016/j.omtm.2019.01.011 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Noguchi, Hirofumi
Miyagi-Shiohira, Chika
Nakashima, Yoshiki
Kinjo, Takao
Kobayashi, Naoya
Saitoh, Issei
Watanabe, Masami
Shapiro, A. M. James
Kin, Tatsuya
Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors
title Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors
title_full Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors
title_fullStr Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors
title_full_unstemmed Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors
title_short Induction of Expandable Tissue-Specific Progenitor Cells from Human Pancreatic Tissue through Transient Expression of Defined Factors
title_sort induction of expandable tissue-specific progenitor cells from human pancreatic tissue through transient expression of defined factors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383192/
https://www.ncbi.nlm.nih.gov/pubmed/30828587
http://dx.doi.org/10.1016/j.omtm.2019.01.011
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