المؤلفون: Asato Sekiya, Ken Takasawa, Yoshikazu Arai, Shin-ichi Horike, Hidenori Akutsu, Akihiro Umezawa, Koichiro Nishino

المصدر: Regenerative Therapy, Vol 21, Iss , Pp 620-630 (2022)

مصطلحات موضوعية: Human iPSCs, Neural stem cells, DNA methylation, Differentiation propensity, Machine learning, Medicine (General), R5-920, Cytology, QH573-671

الوصف: 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.

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352320422001122Test; https://doaj.org/toc/2352-3204Test

الوصول الحر: https://doaj.org/article/713ff3db5b2d4258af590dc1c99b51beTest

المؤلفون: Koichiro Nishino, Yoshikazu Arai

المصدر: The Journal of Toxicological Sciences. 2023, 48(11):571

المؤلفون: Koichiro Nishino, Yoshikazu Arai, Ken Takasawa, Masashi Toyoda, Mayu Yamazaki-Inoue, Tohru Sugawara, Hidenori Akutsu, Ken Nishimura, Manami Ohtaka, Mahito Nakanishi, Akihiro Umezawa

المصدر: Regenerative Therapy, Vol 9, Iss , Pp 71-78 (2018)

مصطلحات موضوعية: Medicine (General), R5-920, Cytology, QH573-671

الوصف: Human induced pluripotent stem cells (iPSCs) are established by introducing several reprogramming factors, such as OCT3/4, SOX2, KLF4, c-MYC. Because of their pluripotency and immortality, iPSCs are considered to be a powerful tool for regenerative medicine. To date, iPSCs have been established all over the world by various gene delivery methods. All methods induced high-quality iPSCs, but epigenetic analysis of abnormalities derived from differences in the gene delivery methods has not yet been performed. Here, we generated genetically matched human iPSCs from menstrual blood cells by using three kinds of vectors, i.e., retrovirus, Sendai virus, and episomal vectors, and compared genome-wide DNA methylation profiles among them. Although comparison of aberrant methylation revealed that iPSCs generated by Sendai virus vector have lowest number of aberrant methylation sites among the three vectors, the iPSCs generated by non-integrating methods did not show vector-specific aberrant methylation. However, the differences between the iPSC lines were determined to be the number of random aberrant hypermethylated regions compared with embryonic stem cells. These random aberrant hypermethylations might be a cause of the differences in the properties of each of the iPSC lines. Keywords: Human iPSCs, Human ESCs, DNA methylation, Aberrant methylation

وصف الملف: electronic resource

العلاقة: http://www.sciencedirect.com/science/article/pii/S2352320418300324Test; https://doaj.org/toc/2352-3204Test

الوصول الحر: https://doaj.org/article/89e5fef2aed349748299b4161679e9d0Test

المؤلفون: Asato SEKIYA, Koichiro NISHINO, Mao TAKAHASHI, Satomi YOSHIDA, Yoshikazu ARAI, 吉田 里美, 新井 良和, 西野 光一郎, 関谷 麻杜, 高橋 真央

المصدر: The Journal of Reproduction and Development Supplement. 2021, :P-43

المؤلفون: Asato SEKIYA, Koichiro NISHINO, Mao TAKAHASHI, Yoshikazu ARAI, 新井 良和, 西野 光一郎, 関谷 麻杜, 高橋 真央

المصدر: The Journal of Reproduction and Development Supplement. 2021, :P-51

المؤلفون: Asato SEKIYA, Koichiro NISHINO, Seira TOMITA, Yoshikazu ARAI, 富田 清良, 新井 良和, 西野 光一郎, 関谷 麻杜

المصدر: The Journal of Reproduction and Development Supplement. 2020, :P-104

المؤلفون: Asato SEKIYA, Ken TAKASAWA, Koichiro NISHINO, Shidow TORISU, Yoshikazu ARAI

المصدر: Journal of Veterinary Medical Science. 2020, 82(6):681

المؤلفون: Hiroshi NAGASHIMA, Hisho FUKUKAWA, Jun OHGANE, Kazuhiro UMEYAMA, Ken TAKASAWA, Kento ONCHI, Koichiro NISHINO, Natsumi OKAZAKI, Yoshikazu ARAI, 大鐘 潤, 岡崎 なつみ, 新井 良和, 梅山 一大, 福川 斐昭, 西野 光一郎, 長嶋 比呂志, 隠地 健斗, 高澤 建

المصدر: The Journal of Reproduction and Development Supplement. 2018, :P-76

المؤلفون: Daigo YOKOI, Koichiro NISHINO, Shoichi WAKITANI, Yuichi HIDAKA

المصدر: Journal of Veterinary Medical Science. 2017, 79(2):230

المؤلفون: Hiroyuki Imai, Kiyoshi Kano, Wataru Fujii, Ken Takasawa, Shoichi Wakitani, Masato Hiyama, Koichiro Nishino, Ken Takeshi Kusakabe, Yasuo Kiso

المصدر: PLoS ONE, Vol 10, Iss 6, p e0130585 (2015)

مصطلحات موضوعية: Medicine, Science

الوصف: Polyploid amphibians and fishes occur naturally in nature, while polyploid mammals do not. For example, tetraploid mouse embryos normally develop into blastocysts, but exhibit abnormalities and die soon after implantation. Thus, polyploidization is thought to be harmful during early mammalian development. However, the mechanisms through which polyploidization disrupts development are still poorly understood. In this study, we aimed to elucidate how genome duplication affects early mammalian development. To this end, we established tetraploid embryonic stem cells (TESCs) produced from the inner cell masses of tetraploid blastocysts using electrofusion of two-cell embryos in mice and studied the developmental potential of TESCs. We demonstrated that TESCs possessed essential pluripotency and differentiation potency to form teratomas, which differentiated into the three germ layers, including diploid embryonic stem cells. TESCs also contributed to the inner cell masses in aggregated chimeric blastocysts, despite the observation that tetraploid embryos fail in normal development soon after implantation in mice. In TESCs, stability after several passages, colony morphology, and alkaline phosphatase activity were similar to those of diploid ESCs. TESCs also exhibited sufficient expression and localization of pluripotent markers and retained the normal epigenetic status of relevant reprogramming factors. TESCs proliferated at a slower rate than ESCs, indicating that the difference in genomic dosage was responsible for the different growth rates. Thus, our findings suggested that mouse ESCs maintained intrinsic pluripotency and differentiation potential despite tetraploidization, providing insights into our understanding of developmental elimination in polyploid mammals.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC4474668?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/60cd8c08f91341058cb98998a16cbf12Test