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Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms

Various culture methods have been developed for maintaining human pluripotent stem cells (PSCs). These PSC maintenance methods exhibit biased differentiation; for example, feeder-dependent PSCs efficiently yield cerebral organoids, but it is difficult to generate organoids from feeder-free PSCs. It...

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Autores principales: Ideno, Hirosato, Imaizumi, Kent, Shimada, Hiroko, Sanosaka, Tsukasa, Nemoto, Akisa, Kohyama, Jun, Okano, Hideyuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9523398/
https://www.ncbi.nlm.nih.gov/pubmed/36185382
http://dx.doi.org/10.1016/j.isci.2022.105140
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author Ideno, Hirosato
Imaizumi, Kent
Shimada, Hiroko
Sanosaka, Tsukasa
Nemoto, Akisa
Kohyama, Jun
Okano, Hideyuki
author_facet Ideno, Hirosato
Imaizumi, Kent
Shimada, Hiroko
Sanosaka, Tsukasa
Nemoto, Akisa
Kohyama, Jun
Okano, Hideyuki
author_sort Ideno, Hirosato
collection PubMed
description Various culture methods have been developed for maintaining human pluripotent stem cells (PSCs). These PSC maintenance methods exhibit biased differentiation; for example, feeder-dependent PSCs efficiently yield cerebral organoids, but it is difficult to generate organoids from feeder-free PSCs. It remains unknown how PSC maintenance conditions affect differentiation. In this study, we identified fibroblast growth factor (FGF) signaling in feeder-free PSC maintenance as a key factor that determines the differentiation toward cerebral organoids. The inhibition of FGF signaling in feeder-free PSCs rescued organoid generation to the same level in feeder-dependent cultures. FGF inhibition induced DNA methylation at the WNT5A locus, and this epigenetic change suppressed the future activation of non-canonical Wnt signaling after differentiation, leading to reliable cerebral organoid generation. This study underscores the importance of PSC culture conditions for directed differentiation into cerebral organoids, and the epigenetic status regulated by FGF signaling is involved in the underlying mechanisms.
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spelling pubmed-95233982022-10-01 Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms Ideno, Hirosato Imaizumi, Kent Shimada, Hiroko Sanosaka, Tsukasa Nemoto, Akisa Kohyama, Jun Okano, Hideyuki iScience Article Various culture methods have been developed for maintaining human pluripotent stem cells (PSCs). These PSC maintenance methods exhibit biased differentiation; for example, feeder-dependent PSCs efficiently yield cerebral organoids, but it is difficult to generate organoids from feeder-free PSCs. It remains unknown how PSC maintenance conditions affect differentiation. In this study, we identified fibroblast growth factor (FGF) signaling in feeder-free PSC maintenance as a key factor that determines the differentiation toward cerebral organoids. The inhibition of FGF signaling in feeder-free PSCs rescued organoid generation to the same level in feeder-dependent cultures. FGF inhibition induced DNA methylation at the WNT5A locus, and this epigenetic change suppressed the future activation of non-canonical Wnt signaling after differentiation, leading to reliable cerebral organoid generation. This study underscores the importance of PSC culture conditions for directed differentiation into cerebral organoids, and the epigenetic status regulated by FGF signaling is involved in the underlying mechanisms. Elsevier 2022-09-16 /pmc/articles/PMC9523398/ /pubmed/36185382 http://dx.doi.org/10.1016/j.isci.2022.105140 Text en © 2022 The Author(s) https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ideno, Hirosato
Imaizumi, Kent
Shimada, Hiroko
Sanosaka, Tsukasa
Nemoto, Akisa
Kohyama, Jun
Okano, Hideyuki
Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms
title Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms
title_full Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms
title_fullStr Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms
title_full_unstemmed Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms
title_short Human PSCs determine the competency of cerebral organoid differentiation via FGF signaling and epigenetic mechanisms
title_sort human pscs determine the competency of cerebral organoid differentiation via fgf signaling and epigenetic mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9523398/
https://www.ncbi.nlm.nih.gov/pubmed/36185382
http://dx.doi.org/10.1016/j.isci.2022.105140
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