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https://hdl.handle.net/20.500.14094/90007297
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2024-04-20
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90007297 (fulltext)
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メタデータID
90007297
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open access
出版タイプ
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タイトル
Retinoic acid receptor gamma activation promotes differentiation of human induced pluripotent stem cells into esophageal epithelium
著者
Koterazawa, Yasufumi ; Koyanagi-Aoi, Michiyo ; Uehara, Keiichiro ; Kakeji, Yoshihiro ; Aoi, Takashi
著者名
Koterazawa, Yasufumi
著者ID
A0443
研究者ID
1000090432327
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=5963935ba79ebd9a520e17560c007669
著者名
Koyanagi-Aoi, Michiyo
青井, 三千代
アオイ, ミチヨ
所属機関名
医学部附属病院
著者ID
A2178
研究者ID
1000070710557
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=28e91fd5fe3c2fef520e17560c007669
著者名
Uehara, Keiichiro
上原, 慶一郎
ウエハラ, ケイイチロウ
所属機関名
医学部附属病院
著者ID
A1706
研究者ID
1000080284488
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=2901d33e92e00ca4520e17560c007669
著者名
Kakeji, Yoshihiro
掛地, 吉弘
カケジ, ヨシヒロ
所属機関名
医学研究科
著者ID
A0444
研究者ID
1000000546997
KUID
https://kuid-rm-web.ofc.kobe-u.ac.jp/search/detail?systemId=fc332006706c5b9e520e17560c007669
著者名
Aoi, Takashi
青井, 貴之
アオイ, タカシ
所属機関名
科学技術イノベーション研究科
収録物名
Journal of Gastroenterology
巻(号)
55(8)
ページ
763-774
出版者
Springer
刊行日
2020-08
公開日
2020-07-27
抄録
Background The esophagus is known to be derived from the foregut. However, the mechanisms regulating this process remain unclear. In particular, the details of the human esophagus itself have been poorly researched. In this decade, studies using human induced pluripotent stem cells (hiPSCs) have proven powerful tools for clarifying the developmental biology of various human organs. Several studies using hiPSCs have demonstrated that retinoic acid (RA) signaling promotes the differentiation of foregut into tissues such as lung and pancreas. However, the effect of RA signaling on the differentiation of foregut into esophagus remains unclear. Methods We established a novel stepwise protocol with transwell culture and an air–liquid interface system for esophageal epithelial cell (EEC) differentiation from hiPSCs. We then evaluated the effect of all-trans retinoic acid (ATRA), which is a retinoic acid receptor (RAR)α, RARβ and RARγ agonist, on the differentiation from the hiPSC-derived foregut. Finally, to identify which RAR subtype was involved in the differentiation, we used synthetic agonists and antagonists of RARα and RARγ, which are known to be expressed in esophagus. Results We successfully generated stratified layers of cells expressing EEC marker genes that were positive for lugol staining. The enhancing effect of ATRA on EEC differentiation was clearly demonstrated with quantitative reverse transcription polymerase chain reaction, immunohistology, lugol-staining and RNA sequencing analyses. RARγ agonist and antagonist enhanced and suppressed EEC differentiation, respectively. RARα agonist had no effect on the differentiation. Conclusion We revealed that RARγ activation promotes the differentiation of hiPSCs-derived foregut into EECs.
キーワード
Induced pluripotent stem cells
Esophageal epithelial cell differentiation
Retinoic acid signal
Retinoic acid receptor γ
カテゴリ
医学研究科
医学部附属病院
科学技術イノベーション研究科
学術雑誌論文
権利
© The Author(s) 2020.
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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/.
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資源タイプ
journal article
言語
English (英語)
ISSN
0944-1174
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eISSN
1435-5922
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NCID
AA10988015
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関連情報
DOI
https://doi.org/10.1007/s00535-020-01695-7
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