ダウンロード数: 123
このアイテムのファイル:
ファイル | 記述 | サイズ | フォーマット | |
---|---|---|---|---|
s41598-017-16858-5.pdf | 4.17 MB | Adobe PDF | 見る/開く |
タイトル: | Adrenergic receptor agonists induce the differentiation of pluripotent stem cell-derived hepatoblasts into hepatocyte-like cells |
著者: | Kotaka, Maki Toyoda, Taro https://orcid.org/0000-0002-2948-0525 (unconfirmed) Yasuda, Katsutaro Kitano, Yuko Okada, Chihiro Ohta, Akira Watanabe, Akira https://orcid.org/0000-0002-4381-4229 (unconfirmed) Uesugi, Motonari Osafune, Kenji https://orcid.org/0000-0001-7238-2763 (unconfirmed) |
著者名の別形: | 小髙, 真希 豊田, 太郎 北野, 優子 岡田, 千尋 渡辺, 亮 上杉, 志成 長船, 健二 |
キーワード: | Pluripotent stem cells Stem-cell differentiation |
発行日: | 1-Dec-2017 |
出版者: | Springer Nature |
誌名: | Scientific Reports |
巻: | 7 |
論文番号: | 16734 |
抄録: | Current induction methods of hepatocytes from human induced pluripotent stem cells (hiPSCs) are neither low cost nor stable. By screening a chemical library of 1, 120 bioactive compounds and known drugs, we identified the α1-adrenergic receptor agonist methoxamine hydrochloride as a small molecule that promotes the differentiation of hiPSC-derived hepatoblasts into ALBUMIN+ hepatocyte-like cells. Other α1-adrenergic receptor agonists also induced the differentiation of hepatocyte-like cells, and an α1-receptor antagonist blocked the hepatic-inducing activity of methoxamine hydrochloride and that of the combination of hepatocyte growth factor (HGF) and Oncostatin M (OsM), two growth factors often used for the induction of hepatoblasts into hepatocyte-like cells. We also confirmed that treatment with methoxamine hydrochloride activates the signal transducer and activator of transcription 3 (STAT3) pathway downstream of IL-6 family cytokines including OsM. These findings allowed us to establish hepatic differentiation protocols for both mouse embryonic stem cells (mESCs) and hiPSCs using small molecules at the step from hepatoblasts into hepatocyte-like cells. The results of the present study suggest that α1-adrenergic agonists induce hepatocyte-like cells by working downstream of HGF and OsM to activate STAT3. |
著作権等: | © The Author(s) 2017. 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/. |
URI: | http://hdl.handle.net/2433/246542 |
DOI(出版社版): | 10.1038/s41598-017-16858-5 |
PubMed ID: | 29196668 |
出現コレクション: | 学術雑誌掲載論文等 |
このリポジトリに保管されているアイテムはすべて著作権により保護されています。