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Article

Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic Stem Cell-Derived Spheres

1
Laboratory of Kampo Pharmacology, Yokohama University of Pharmacy, Yokohama 245-0066, Japan
2
Liver Cancer Prevention Research Unit, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan
3
Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan
4
Department of Psychiatry and Behavioral Science, Kanazawa University School of Medicine, Kanazawa, Ishikawa 920-0942, Japan
5
Environmental Health and Prevention Research Unit, Yokohama University of Pharmacy, Yokohama 245-0066, Japan
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(15), 5564; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155564
Received: 18 June 2020 / Revised: 22 July 2020 / Accepted: 30 July 2020 / Published: 3 August 2020
(This article belongs to the Special Issue Psychoactive Substances in Neuronal Development)
Stress in early life has been linked with the development of late-life neurological disorders. Early developmental age is potentially sensitive to several environmental chemicals such as alcohol, drugs, food contaminants, or air pollutants. The recent advances using three-dimensional neural sphere cultures derived from pluripotent stem cells have provided insights into the etiology of neurological diseases and new therapeutic strategies for assessing chemical safety. In this study, we investigated the neurodevelopmental effects of exposure to thalidomide (TMD); 2,2′,4,4′-tetrabromodiphenyl ether; bisphenol A; and 4-hydroxy-2,2′,3,4′,5,5′,6-heptachlorobiphenyl using a human embryonic stem cell (hESC)-derived sphere model. We exposed each chemical to the spheres and conducted a combinational analysis of global gene expression profiling using microarray at the early stage and morphological examination of neural differentiation at the later stage to understand the molecular events underlying the development of hESC-derived spheres. Among the four chemicals, TMD exposure especially influenced the differentiation of spheres into neuronal cells. Transcriptomic analysis and functional annotation identified specific genes that are TMD-induced and associated with ERK and synaptic signaling pathways. Computational network analysis predicted that TMD induced the expression of DNA-binding protein inhibitor ID2, which plays an important role in neuronal development. These findings provide direct evidence that early transcriptomic changes during differentiation of hESCs upon exposure to TMD influence neuronal development in the later stages. View Full-Text
Keywords: thalidomide; environmental chemicals; neuronal differentiations; human embryonic stem cells; computational network analysis thalidomide; environmental chemicals; neuronal differentiations; human embryonic stem cells; computational network analysis
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MDPI and ACS Style

Kikegawa, M.; Qin, X.-Y.; Ito, T.; Nishikawa, H.; Nansai, H.; Sone, H. Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic Stem Cell-Derived Spheres. Int. J. Mol. Sci. 2020, 21, 5564. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155564

AMA Style

Kikegawa M, Qin X-Y, Ito T, Nishikawa H, Nansai H, Sone H. Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic Stem Cell-Derived Spheres. International Journal of Molecular Sciences. 2020; 21(15):5564. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155564

Chicago/Turabian Style

Kikegawa, Mami, Xian-Yang Qin, Tomohiro Ito, Hiromi Nishikawa, Hiroko Nansai, and Hideko Sone. 2020. "Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic Stem Cell-Derived Spheres" International Journal of Molecular Sciences 21, no. 15: 5564. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21155564

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