Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids
Abstract The effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radia...
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| Format: | Article |
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Nature Portfolio
2023-08-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-023-40051-6 |
| _version_ | 1797453210916487168 |
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| author | Mari Katsura Yoshihiro Urade Hiroko Nansai Mika Kobayashi Akashi Taguchi Yukiko Ishikawa Tomohiro Ito Hisako Fukunaga Hideto Tozawa Yoko Chikaoka Ryo Nakaki Akinobu Echigo Takahide Kohro Hideko Sone Youichiro Wada |
| author_facet | Mari Katsura Yoshihiro Urade Hiroko Nansai Mika Kobayashi Akashi Taguchi Yukiko Ishikawa Tomohiro Ito Hisako Fukunaga Hideto Tozawa Yoko Chikaoka Ryo Nakaki Akinobu Echigo Takahide Kohro Hideko Sone Youichiro Wada |
| author_sort | Mari Katsura |
| collection | DOAJ |
| description | Abstract The effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radiation and predicted their changes. Developing retinal cells generated from human induced pluripotent stem cells (iPSCs) were irradiated with either 30 or 180 mGy on days 4–5 of development for 24 h. Genome-wide gene expression was observed until day 35. A knowledge-based pathway analysis algorithm revealed fluctuations in Rho signaling and many other pathways. After a month, the levels of an essential transcription factor of eye development, the proportion of paired box 6 (PAX6)-positive cells, and the proportion of retinal ganglion cell (RGC)-specific transcription factor POU class 4 homeobox 2 (POU4F2)-positive cells increased with 30 mGy of irradiation. In contrast, they decreased after 180 mGy of irradiation. Activation of the “development of neurons” pathway after 180 mGy indicated the dedifferentiation and development of other neural cells. Fluctuating effects after low-dose radiation exposure suggest that developing retinal cells employ hormesis and dedifferentiation mechanisms in response to stress. |
| first_indexed | 2024-03-09T15:19:30Z |
| format | Article |
| id | doaj.art-6849065892ea40a1a85340298c3e35b4 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-09T15:19:30Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-6849065892ea40a1a85340298c3e35b42023-11-26T12:52:19ZengNature PortfolioScientific Reports2045-23222023-08-0113111310.1038/s41598-023-40051-6Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoidsMari Katsura0Yoshihiro Urade1Hiroko Nansai2Mika Kobayashi3Akashi Taguchi4Yukiko Ishikawa5Tomohiro Ito6Hisako Fukunaga7Hideto Tozawa8Yoko Chikaoka9Ryo Nakaki10Akinobu Echigo11Takahide Kohro12Hideko Sone13Youichiro Wada14Isotope Science Center, The University of TokyoIsotope Science Center, The University of TokyoGraduate School of Medicine and Faculty of Medicine, The University of TokyoIsotope Science Center, The University of TokyoIsotope Science Center, The University of TokyoIsotope Science Center, The University of TokyoCenter for Health and Environmental Risk Research, National Institute for Environmental StudiesGraduate School of Medicine and Faculty of Medicine, The University of TokyoGraduate School of Science, The University of TokyoIsotope Science Center, The University of TokyoRhelixa Co., LtdTomy Digital Biology Co., LtdDepartment of Clinical Informatics, Jichi Medical UniversityCenter for Health and Environmental Risk Research, National Institute for Environmental StudiesIsotope Science Center, The University of TokyoAbstract The effects of low-dose radiation on undifferentiated cells carry important implications. However, the effects on developing retinal cells remain unclear. Here, we analyzed the gene expression characteristics of neuronal organoids containing immature human retinal cells under low-dose radiation and predicted their changes. Developing retinal cells generated from human induced pluripotent stem cells (iPSCs) were irradiated with either 30 or 180 mGy on days 4–5 of development for 24 h. Genome-wide gene expression was observed until day 35. A knowledge-based pathway analysis algorithm revealed fluctuations in Rho signaling and many other pathways. After a month, the levels of an essential transcription factor of eye development, the proportion of paired box 6 (PAX6)-positive cells, and the proportion of retinal ganglion cell (RGC)-specific transcription factor POU class 4 homeobox 2 (POU4F2)-positive cells increased with 30 mGy of irradiation. In contrast, they decreased after 180 mGy of irradiation. Activation of the “development of neurons” pathway after 180 mGy indicated the dedifferentiation and development of other neural cells. Fluctuating effects after low-dose radiation exposure suggest that developing retinal cells employ hormesis and dedifferentiation mechanisms in response to stress.https://doi.org/10.1038/s41598-023-40051-6 |
| spellingShingle | Mari Katsura Yoshihiro Urade Hiroko Nansai Mika Kobayashi Akashi Taguchi Yukiko Ishikawa Tomohiro Ito Hisako Fukunaga Hideto Tozawa Yoko Chikaoka Ryo Nakaki Akinobu Echigo Takahide Kohro Hideko Sone Youichiro Wada Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids Scientific Reports |
| title | Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids |
| title_full | Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids |
| title_fullStr | Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids |
| title_full_unstemmed | Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids |
| title_short | Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids |
| title_sort | low dose radiation induces unstable gene expression in developing human ipsc derived retinal ganglion organoids |
| url | https://doi.org/10.1038/s41598-023-40051-6 |
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