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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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Autores principales: Tsuzuki, Syusaku, Yamaguchi, Tomoyuki, Okumura, Takashi, Kasai, Toshiharu, Ueno, Yasuharu, Taniguchi, Hideki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138705/
https://www.ncbi.nlm.nih.gov/pubmed/37108241
http://dx.doi.org/10.3390/ijms24087075
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author Tsuzuki, Syusaku
Yamaguchi, Tomoyuki
Okumura, Takashi
Kasai, Toshiharu
Ueno, Yasuharu
Taniguchi, Hideki
author_facet Tsuzuki, Syusaku
Yamaguchi, Tomoyuki
Okumura, Takashi
Kasai, Toshiharu
Ueno, Yasuharu
Taniguchi, Hideki
author_sort Tsuzuki, Syusaku
collection PubMed
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 PDGFRA 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 PDGFRA 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.
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spelling pubmed-101387052023-04-28 PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids Tsuzuki, Syusaku Yamaguchi, Tomoyuki Okumura, Takashi Kasai, Toshiharu Ueno, Yasuharu Taniguchi, Hideki Int J Mol Sci Article 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 PDGFRA 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 PDGFRA 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. MDPI 2023-04-11 /pmc/articles/PMC10138705/ /pubmed/37108241 http://dx.doi.org/10.3390/ijms24087075 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tsuzuki, Syusaku
Yamaguchi, Tomoyuki
Okumura, Takashi
Kasai, Toshiharu
Ueno, Yasuharu
Taniguchi, Hideki
PDGF Receptors and Signaling Are Required for 3D-Structure Formation and Differentiation of Human iPSC-Derived Hepatic Spheroids
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138705/
https://www.ncbi.nlm.nih.gov/pubmed/37108241
http://dx.doi.org/10.3390/ijms24087075
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