ID 57241
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Noguchi, Hirofumi Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus
Miyagi-Shiohira, Chika Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus
Nakashima, Yoshiki Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus
Kinjo, Takao Department of Basic Laboratory Sciences, School of Health Sciences in Faculty of Medicine, University of the Ryukyus
Kobayashi, Naoya Okayama Saidaiji Hospital
Saitoh, Issei Division of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University
Watanabe, Masami Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences Kaken ID publons researchmap
Shapiro, A. M. James Clinical Islet Transplant Program and Department of Surgery, University of Alberta
Kin, Tatsuya Clinical Islet Transplant Program and Department of Surgery, University of Alberta
Abstract
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.
Keywords
induced tissue-specific progenitor cells
iTP
induced tissue-specific stem cells
iTS
induced pluripotent stem cells
iPSCs
reprogramming factors
pancreas
Published Date
2019-06-14
Publication Title
Molecular Therapy - Methods and Clinical Development
Volume
volume13
Publisher
Cell Press
Start Page
243
End Page
252
ISSN
2329-0501
Content Type
Journal Article
language
英語
OAI-PMH Set
岡山大学
Copyright Holders
© 2019 The Author(s).
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DOI
Web of Science KeyUT
Related Url
isVersionOf https://doi.org/10.1016/j.omtm.2019.01.011
License
http://creativecommons.org/licenses/by/4.0/
Funder Name
Japan Society for the Promotion of Science
助成番号
JP16H05404
JP16K10435
JP18K08545
JP15H04297
JP16K15689