PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids
Human iPSC-derived liver organoids (LO) or hepatic spheroids (HS) have attracted widespread interest, and the numerous studies on them have recently provided various production protocols. However, the mechanism by which the 3D structures of LO and HS are formed from the 2D-cultured cells and the mec...
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| Format: | Article |
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MDPI AG
2023-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/8/7075 |
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| author | Syusaku Tsuzuki Tomoyuki Yamaguchi Takashi Okumura Toshiharu Kasai Yasuharu Ueno Hideki Taniguchi |
| author_facet | Syusaku Tsuzuki Tomoyuki Yamaguchi Takashi Okumura Toshiharu Kasai Yasuharu Ueno Hideki Taniguchi |
| author_sort | Syusaku Tsuzuki |
| collection | DOAJ |
| description | Human iPSC-derived liver organoids (LO) or hepatic spheroids (HS) have attracted widespread interest, and the numerous studies on them have recently provided various production protocols. However, the mechanism by which the 3D structures of LO and HS are formed from the 2D-cultured cells and the mechanism of the LO and HS maturation remain largely unknown. In this study, we demonstrate that <i>PDGFRA</i> is specifically induced in the cells that are suitable for HS formation and that PDGF receptors and signaling are required for HS formation and maturation. Additionally, in vivo, we show that the localization of PDGFRα is in complete agreement with mouse E9.5 hepatoblasts, which begin to form the 3D-structural liver bud from the single layer. Our results present that <i>PDGFRA</i> play important roles for 3D structure formation and maturation of hepatocytes in vitro and in vivo and provide a clue to elucidate the hepatocyte differentiation mechanism. |
| first_indexed | 2024-03-11T04:57:16Z |
| format | Article |
| id | doaj.art-8c01c6dd304a4f0b989baaf06148fbb1 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:57:16Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-8c01c6dd304a4f0b989baaf06148fbb12023-11-17T19:34:54ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-04-01248707510.3390/ijms24087075PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic SpheroidsSyusaku Tsuzuki0Tomoyuki Yamaguchi1Takashi Okumura2Toshiharu Kasai3Yasuharu Ueno4Hideki Taniguchi5Division of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-0071, JapanLaboratory of Regenerative Medicine, Tokyo University of Pharmacy and Life Science, Tokyo 192-0392, JapanDivision of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-0071, JapanDivision of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-0071, JapanDivision of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-0071, JapanDivision of Regenerative Medicine, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo 108-0071, JapanHuman iPSC-derived liver organoids (LO) or hepatic spheroids (HS) have attracted widespread interest, and the numerous studies on them have recently provided various production protocols. However, the mechanism by which the 3D structures of LO and HS are formed from the 2D-cultured cells and the mechanism of the LO and HS maturation remain largely unknown. In this study, we demonstrate that <i>PDGFRA</i> is specifically induced in the cells that are suitable for HS formation and that PDGF receptors and signaling are required for HS formation and maturation. Additionally, in vivo, we show that the localization of PDGFRα is in complete agreement with mouse E9.5 hepatoblasts, which begin to form the 3D-structural liver bud from the single layer. Our results present that <i>PDGFRA</i> play important roles for 3D structure formation and maturation of hepatocytes in vitro and in vivo and provide a clue to elucidate the hepatocyte differentiation mechanism.https://www.mdpi.com/1422-0067/24/8/7075human iPSC3D cultureliver organoidshepatic spheroidsplatelet-derived growth factors (PDGFs)PDGF receptors |
| spellingShingle | Syusaku Tsuzuki Tomoyuki Yamaguchi Takashi Okumura Toshiharu Kasai Yasuharu Ueno Hideki Taniguchi PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids International Journal of Molecular Sciences human iPSC 3D culture liver organoids hepatic spheroids platelet-derived growth factors (PDGFs) PDGF receptors |
| title | PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids |
| title_full | PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids |
| title_fullStr | PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids |
| title_full_unstemmed | PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids |
| title_short | PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids |
| title_sort | pdgf receptors and signaling are required for 3d structure formation and differentiation of human ipsc derived hepatic spheroids |
| topic | human iPSC 3D culture liver organoids hepatic spheroids platelet-derived growth factors (PDGFs) PDGF receptors |
| url | https://www.mdpi.com/1422-0067/24/8/7075 |
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