{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:06:31Z","timestamp":1760238391183,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,8,3]],"date-time":"2020-08-03T00:00:00Z","timestamp":1596412800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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\u2032,4,4\u2032-tetrabromodiphenyl ether; bisphenol A; and 4-hydroxy-2,2\u2032,3,4\u2032,5,5\u2032,6-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.<\/jats:p>","DOI":"10.3390\/ijms21155564","type":"journal-article","created":{"date-parts":[[2020,8,4]],"date-time":"2020-08-04T05:56:46Z","timestamp":1596520606000},"page":"5564","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Early Transcriptomic Changes upon Thalidomide Exposure Influence the Later Neuronal Development in Human Embryonic Stem Cell-Derived Spheres"],"prefix":"10.3390","volume":"21","author":[{"given":"Mami","family":"Kikegawa","sequence":"first","affiliation":[{"name":"Laboratory of Kampo Pharmacology, Yokohama University of Pharmacy, Yokohama 245-0066, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0110-6849","authenticated-orcid":false,"given":"Xian-Yang","family":"Qin","sequence":"additional","affiliation":[{"name":"Liver Cancer Prevention Research Unit, RIKEN Cluster for Pioneering Research, Wako, Saitama 351-0198, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomohiro","family":"Ito","sequence":"additional","affiliation":[{"name":"Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiromi","family":"Nishikawa","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Science, Kanazawa University School of Medicine, Kanazawa, Ishikawa 920-0942, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroko","family":"Nansai","sequence":"additional","affiliation":[{"name":"Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7162-6455","authenticated-orcid":false,"given":"Hideko","family":"Sone","sequence":"additional","affiliation":[{"name":"Laboratory of Kampo Pharmacology, Yokohama University of Pharmacy, Yokohama 245-0066, Japan"},{"name":"Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba, Ibaraki 305-8506, Japan"},{"name":"Environmental Health and Prevention Research Unit, Yokohama University of Pharmacy, Yokohama 245-0066, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1553","DOI":"10.1016\/S0140-6736(18)31612-X","article-title":"The Lancet Commission on global mental health and sustainable development","volume":"392","author":"Patel","year":"2018","journal-title":"Lancet"},{"key":"ref_2","first-page":"1","article-title":"Estimated Prevalence of Autism and Other Developmental Disabilities Following Questionnaire Changes in the 2014 National Health Interview Survey","volume":"13","author":"Zablotsky","year":"2015","journal-title":"Natl. 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