RRC ID 76707
著者 Katsura M, Urade Y, Nansai H, Kobayashi M, Taguchi A, Ishikawa Y, Ito T, Fukunaga H, Tozawa H, Chikaoka Y, Nakaki R, Echigo A, Kohro T, Sone H, Wada Y.
タイトル Low-dose radiation induces unstable gene expression in developing human iPSC-derived retinal ganglion organoids.
ジャーナル Sci Rep
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.
巻・号 13(1)
ページ 12888
公開日 2023-8-9
DOI 10.1038/s41598-023-40051-6
PII 10.1038/s41598-023-40051-6
PMID 37558727
PMC PMC10412642
MeSH Cell Differentiation Gene Expression Humans Induced Pluripotent Stem Cells* / metabolism Organoids Retina / metabolism Retinal Ganglion Cells* / metabolism
IF 3.998
リソース情報
ヒト・動物細胞 201B7(HPS0063)