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Variation of DNA methylation on the IRX1/2 genes is responsible for the neural differentiation propensity in human induced pluripotent stem cells
http://hdl.handle.net/10458/00010466
http://hdl.handle.net/10458/00010466ab7aa9b6-a1cc-4fa3-b33f-656fd9a0c465
| 名前 / ファイル | ライセンス | アクション |
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本文 (3.6 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2023-01-24 | |||||
| タイトル | ||||||
| タイトル | Variation of DNA methylation on the IRX1/2 genes is responsible for the neural differentiation propensity in human induced pluripotent stem cells | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Human iPSCs | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Neural stem cells | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | DNA methylation | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Differentiation propensity | |||||
| キーワード | ||||||
| 言語 | en | |||||
| 主題Scheme | Other | |||||
| キーワード | Machine learning | |||||
| 資源タイプ | ||||||
| 資源タイプ | journal article | |||||
| 著者 |
新井, 良和
× 新井, 良和× 西野, 光一郎× Sekiya, Asato× Takasawa, Ken× Arai, Yoshikazu× Horike, Shin-ichi× Akutsu, Hidenori× Umezawa, Akihiro× Nishino, Koichiro |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Introduction Human induced pluripotent stem cells （hiPSCs） are useful tools for reproducing neural development in vitro. However, each hiPSC line has a different ability to differentiate into specific lineages, known as differentiation propensity, resulting in reduced reproducibility and increased time and funding requirements for research. To overcome this issue, we searched for predictive signatures of neural differentiation propensity of hiPSCs focusing on DNA methylation, which is the main modulator of cellular properties. Methods We obtained 32 hiPSC lines and their comprehensive DNA methylation data using the Infinium MethylationEPIC BeadChip. To assess the neural differentiation efficiency of these hiPSCs, we measured the percentage of neural stem cells on day 7 of induction. Using the DNA methylation data of undifferentiated hiPSCs and their measured differentiation efficiency into neural stem cells as the set of data, and HSIC Lasso, a machine learning-based nonlinear feature selection method, we attempted to identify neural differentiation-associated differentially methylated sites. Results Epigenome-wide unsupervised clustering cannot distinguish hiPSCs with varying differentiation efficiencies. In contrast, HSIC Lasso identified 62 CpG sites that could explain the neural differentiation efficiency of hiPSCs. Features selected by HSIC Lasso were particularly enriched within 3 Mbp of chromosome 5, harboring IRX1, IRX2, and C5orf38 genes. Within this region, DNA methylation rates were correlated with neural differentiation efficiency and were negatively correlated with gene expression of the IRX1/2 genes, particularly in female hiPSCs. In addition, forced expression of the IRX1/2 impaired the neural differentiation ability of hiPSCs in both sexes. Conclusion We for the first time showed that the DNA methylation state of the IRX1/2 genes of hiPSCs is a predictive biomarker of their potential for neural differentiation. The predictive markers for neural differentiation efficiency identified in this study may be useful for the selection of suitable undifferentiated hiPSCs prior to differentiation induction. |
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| 書誌情報 |
en : Regenerative Therapy 巻 21, p. 620-630, 発行日 2022 |
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| 出版者 | ||||||
| 出版者 | Elsevier | |||||
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| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 23523204 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1016/j.reth.2022.11.007 | |||||
| 権利 | ||||||
| 権利情報 | © 2022 The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. | |||||
| フォーマット | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | application/pdf | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
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新井, 良和, 西野, 光一郎, Sekiya, Asato, Takasawa, Ken, Arai, Yoshikazu, Horike, Shin-ichi, Akutsu, Hidenori, Umezawa, Akihiro, Nishino, Koichiro, 2022, Variation of DNA methylation on the IRX1/2 genes is responsible for the neural differentiation propensity in human induced pluripotent stem cells: Elsevier, 620–630 p.
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