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Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids.
Katsura, Mari; Urade, Yoshihiro; Nansai, Hiroko; Kobayashi, Mika; Taguchi, Akashi; Ishikawa, Yukiko; Ito, Tomohiro; Fukunaga, Hisako; Tozawa, Hideto; Chikaoka, Yoko; Nakaki, Ryo; Echigo, Akinobu; Kohro, Takahide; Sone, Hideko; Wada, Youichiro.
Afiliación
  • Katsura M; Isotope Science Center, The University of Tokyo, Tokyo, Japan.
  • Urade Y; Reiwa Eye Clinic, Hatsukaichi, Hiroshima, Japan.
  • Nansai H; Isotope Science Center, The University of Tokyo, Tokyo, Japan.
  • Kobayashi M; Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
  • Taguchi A; Isotope Science Center, The University of Tokyo, Tokyo, Japan.
  • Ishikawa Y; Isotope Science Center, The University of Tokyo, Tokyo, Japan.
  • Ito T; Isotope Science Center, The University of Tokyo, Tokyo, Japan.
  • Fukunaga H; Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan.
  • Tozawa H; Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
  • Chikaoka Y; Graduate School of Science, The University of Tokyo, Tokyo, Japan.
  • Nakaki R; Isotope Science Center, The University of Tokyo, Tokyo, Japan.
  • Echigo A; Rhelixa Co., Ltd, Tokyo, Japan.
  • Kohro T; Tomy Digital Biology Co., Ltd, Tokyo, Japan.
  • Sone H; Department of Clinical Informatics, Jichi Medical University, Shimotsuke, Tochigi, Japan.
  • Wada Y; Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Ibaraki, Japan. hideko.sone@yok.hamayaku.ac.jp.
Sci Rep ; 13(1): 12888, 2023 08 09.
Article en En | MEDLINE | ID: mdl-37558727
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Ganglionares de la Retina / Células Madre Pluripotentes Inducidas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Ganglionares de la Retina / Células Madre Pluripotentes Inducidas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Japón Pais de publicación: Reino Unido