Induced hepatic stem cells are suitable for human hepatocyte production

Summary: Human hepatocytes were transfected with Sendai virus vectors (SeV) expressing OCT3/4, SOX2, KLF4, and C-MYC to produce hepatocyte-derived induced pluripotent stem cells (iPSCs). The messenger RNA (mRNA) expression of undifferentiated markers (passage 19-21) and hepatocyte-specific markers (...

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Main Authors: Yoshiki Nakashima, Chika Miyagi-Shiohira, Issei Saitoh, Masami Watanabe, Masayuki Matsushita, Masayoshi Tsukahara, Hirofumi Noguchi
Format: Article
Language:English
Published: Elsevier 2022-10-01
Series:iScience
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2589004222013244
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author Yoshiki Nakashima
Chika Miyagi-Shiohira
Issei Saitoh
Masami Watanabe
Masayuki Matsushita
Masayoshi Tsukahara
Hirofumi Noguchi
author_facet Yoshiki Nakashima
Chika Miyagi-Shiohira
Issei Saitoh
Masami Watanabe
Masayuki Matsushita
Masayoshi Tsukahara
Hirofumi Noguchi
author_sort Yoshiki Nakashima
collection DOAJ
description Summary: Human hepatocytes were transfected with Sendai virus vectors (SeV) expressing OCT3/4, SOX2, KLF4, and C-MYC to produce hepatocyte-derived induced pluripotent stem cells (iPSCs). The messenger RNA (mRNA) expression of undifferentiated markers (passage 19-21) and hepatocyte-specific markers (HSMs) (passage 0-20) in 48 established hepatocyte-derived iPSC-like colonies was examined. Among the 48 clones, 10 clones continuously expressed HSM mRNA (HNF1β and HNF4α) in passage 0-20. The colonies which expressed HSMs (iTS-L cells: induced tissue-specific stem cells from liver) showed a different tendency in microarray and methylation analyses to fibroblast-derived iPSCs (strain: 201B7). iTS-L cells were less likely to form teratomas in mice than iPSCs (He). The iTS-L cells were differentiated into hepatocyte-like cells more efficiently than iPSCs (He) or iPSCs (201B7). These data suggest that SeV expressing OCT3/4, SOX2, KLF4, and C-MYC induce the generation of iPSCs and iTS-L cells.
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spelling doaj.art-154522eb098b4816be1c681a09bfda0f2022-12-22T03:20:07ZengElsevieriScience2589-00422022-10-012510105052Induced hepatic stem cells are suitable for human hepatocyte productionYoshiki Nakashima0Chika Miyagi-Shiohira1Issei Saitoh2Masami Watanabe3Masayuki Matsushita4Masayoshi Tsukahara5Hirofumi Noguchi6Department of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan; Kyoto University Center for iPS Cell Research and Application Foundation (CiRA Foundation), Facility for iPS Cell Therapy (FiT), Kyoto 606-8397, JapanDepartment of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, JapanDivision of Pediatric Dentistry, Graduate School of Medical and Dental Science, Niigata University, Niigata 951-8514, JapanDepartment of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, JapanDepartment of Molecular and Cellular Physiology, Graduate School of Medicine, University of the Ryukyus, Okinawa 903-0215, JapanKyoto University Center for iPS Cell Research and Application Foundation (CiRA Foundation), Facility for iPS Cell Therapy (FiT), Kyoto 606-8397, JapanDepartment of Regenerative Medicine, Graduate School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan; CorrespondingSummary: Human hepatocytes were transfected with Sendai virus vectors (SeV) expressing OCT3/4, SOX2, KLF4, and C-MYC to produce hepatocyte-derived induced pluripotent stem cells (iPSCs). The messenger RNA (mRNA) expression of undifferentiated markers (passage 19-21) and hepatocyte-specific markers (HSMs) (passage 0-20) in 48 established hepatocyte-derived iPSC-like colonies was examined. Among the 48 clones, 10 clones continuously expressed HSM mRNA (HNF1β and HNF4α) in passage 0-20. The colonies which expressed HSMs (iTS-L cells: induced tissue-specific stem cells from liver) showed a different tendency in microarray and methylation analyses to fibroblast-derived iPSCs (strain: 201B7). iTS-L cells were less likely to form teratomas in mice than iPSCs (He). The iTS-L cells were differentiated into hepatocyte-like cells more efficiently than iPSCs (He) or iPSCs (201B7). These data suggest that SeV expressing OCT3/4, SOX2, KLF4, and C-MYC induce the generation of iPSCs and iTS-L cells.http://www.sciencedirect.com/science/article/pii/S2589004222013244Humanbiological sciencescell biologystem cells researchdevelopmental biology
spellingShingle Yoshiki Nakashima
Chika Miyagi-Shiohira
Issei Saitoh
Masami Watanabe
Masayuki Matsushita
Masayoshi Tsukahara
Hirofumi Noguchi
Induced hepatic stem cells are suitable for human hepatocyte production
iScience
Human
biological sciences
cell biology
stem cells research
developmental biology
title Induced hepatic stem cells are suitable for human hepatocyte production
title_full Induced hepatic stem cells are suitable for human hepatocyte production
title_fullStr Induced hepatic stem cells are suitable for human hepatocyte production
title_full_unstemmed Induced hepatic stem cells are suitable for human hepatocyte production
title_short Induced hepatic stem cells are suitable for human hepatocyte production
title_sort induced hepatic stem cells are suitable for human hepatocyte production
topic Human
biological sciences
cell biology
stem cells research
developmental biology
url http://www.sciencedirect.com/science/article/pii/S2589004222013244
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AT isseisaitoh inducedhepaticstemcellsaresuitableforhumanhepatocyteproduction
AT masamiwatanabe inducedhepaticstemcellsaresuitableforhumanhepatocyteproduction
AT masayukimatsushita inducedhepaticstemcellsaresuitableforhumanhepatocyteproduction
AT masayoshitsukahara inducedhepaticstemcellsaresuitableforhumanhepatocyteproduction
AT hirofuminoguchi inducedhepaticstemcellsaresuitableforhumanhepatocyteproduction