{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T15:26:15Z","timestamp":1787412375200,"version":"build-2736575974"},"reference-count":27,"publisher":"American Chemical Society (ACS)","issue":"8","license":[{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22476209"],"award-info":[{"award-number":["22476209"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22576225"],"award-info":[{"award-number":["22576225"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","award":["XDB0750300"],"award-info":[{"award-number":["XDB0750300"]}],"id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Humans are frequently exposed to diverse environmental pollutants that may pose potential risks during early embryonic development. Advances in stem cell toxicology have introduced new opportunities for environmental toxicity assessment, enabling the development of physiologically relevant models based on human induced pluripotent stem cells (iPSCs). However, current systems remain limited by low throughput and the inability to achieve real-time monitoring. In this study, we established a NANOG-EGFP iPSC reporter line by precisely inserting a T2A-EGFP cassette into the endogenous NANOG locus using CRISPR\/Cas9, enabling dynamic and quantitative visualization of pluripotency status. Using this reporter system, we systematically evaluated the effects of 38 representative environmental pollutants spanning six major chemical categories, including bisphenols, per- and polyfluoroalkyl substances (PFAS), halogenated flame retardants, organophosphate esters, neonicotinoids, and phenolic compounds. Most pollutants induced varying degrees of reduction in NANOG-EGFP expression, suggesting perturbation of core transcriptional networks involved in pluripotency maintenance rather than nonspecific cytotoxic effects. Notably, bisphenol B (BPB), bisphenol Z (BPZ), perfluorobutanesulfonic acid (PFBS), tributyl phosphate (TnBP), tris(2-chloroethyl) phosphate (TCEP), and 3,5-di-tert-butyl-4-hydroxybenzoic acid (BHT-COOH) exhibited pronounced low-dose activity, causing significant suppression of NANOG-EGFP signals even at 10 nmol\/L. Furthermore, during neuroectoderm differentiation, several bisphenols and PFAS delayed the normal downregulation of NANOG, indicating disruption of the tightly regulated timing of pluripotency exit and lineage transition during early developmental progression. Overall, the NANOG-EGFP iPSC reporter model provides a sensitive, stable, and practical platform for high-throughput screening of environmental toxicants and offers mechanistically informed insight into how pollutant exposure may interfere with early human developmental regulatory programs.<\/jats:p>","DOI":"10.1021\/envhealth.5c00797","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T14:48:46Z","timestamp":1775054926000},"page":"1732-1740","source":"Crossref","is-referenced-by-count":0,"title":["A\n                    <i>NANOG<\/i>\n                    -\n                    <i>EGFP<\/i>\n                    iPSC-Based\nReporter Platform for High-Throughput Screening of Environmental Pollutant\nEffects on Pluripotency"],"prefix":"10.1021","volume":"4","author":[{"given":"Yanyi","family":"Zhao","sequence":"first","affiliation":[{"name":"Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanyue","family":"Li","sequence":"additional","affiliation":[{"name":"Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9353-5041","authenticated-orcid":true,"given":"Renjun","family":"Yang","sequence":"additional","affiliation":[{"name":"Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1715-5255","authenticated-orcid":true,"given":"Nuoya","family":"Yin","sequence":"additional","affiliation":[{"name":"Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3512-8253","authenticated-orcid":true,"given":"Francesco","family":"Faiola","sequence":"additional","affiliation":[{"name":"Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences , , ,","place":["Beijing, China, 100085"]},{"name":"University of Chinese Academy of Sciences , , ,","place":["Beijing, China, 100049"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"issue":"9","key":"2026082211091836100_cit1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e19496","article-title":"Environmental\npollutants and their effects on human health","volume":"9","author":"Shetty","year":"2023","journal-title":"Heliyon"},{"key":"2026082211091836100_cit2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms232214271","article-title":"Studying the Impact\nof Persistent Organic Pollutants\nExposure on Human Health by Proteomic Analysis: A Systematic Review","volume":"23","author":"Guillotin","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2026082211091836100_cit3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhazmat.2024.133906","article-title":"Biodegradation of phenolic\npollutants and bioaugmentation strategies: A review of current knowledge\nand future perspectives","volume":"469","author":"Wang","year":"2024","journal-title":"Journal of Hazardous\nMaterials"},{"key":"2026082211091836100_cit4","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2024.118955","article-title":"Exposure to\norganophosphate esters and maternal-child health","volume":"252","author":"Shahin","year":"2024","journal-title":"Environmental Research"},{"key":"2026082211091836100_cit5","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2022.107201","article-title":"Human exposure to neonicotinoids\nand the associated health risks:\nA review","volume":"163","author":"Zhang","year":"2022","journal-title":"Environ. Int."},{"key":"2026082211091836100_cit6","doi-asserted-by":"publisher","DOI":"10.1021\/envhealth.5c00628","article-title":"Insights into\nthe Neurotoxicology\nof Traditional and Emerging Per- and Polyfluoroalkyl Substances: Mechanisms\nand Research Frontiers","author":"Ren","year":"2026","journal-title":"Environ. Health"},{"key":"2026082211091836100_cit7","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2021.111531","article-title":"Analysis, occurrence, toxicity and\nenvironmental health risks of\nsynthetic phenolic antioxidants: A review","volume":"201","author":"Wang","year":"2021","journal-title":"Environmental\nResearch"},{"key":"2026082211091836100_cit8","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2019.108575","article-title":"The adverse\nhealth effects of bisphenol A and related toxicity mechanisms","volume":"176","author":"Ma","year":"2019","journal-title":"Environmental Research"},{"key":"2026082211091836100_cit9","doi-asserted-by":"publisher","first-page":"5847","DOI":"10.1021\/acs.est.5b01549","article-title":"The rise of\nstem cell toxicology","volume":"49","author":"Faiola","year":"2015","journal-title":"Environ. Sci. 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Mol. Cellular Toxicol."},{"issue":"1","key":"2026082211091836100_cit14","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1038\/sj.cr.7310125","article-title":"Nanog and transcriptional networks in embryonic stem\ncell pluripotency","volume":"17","author":"Pan","year":"2007","journal-title":"Cell Research"},{"issue":"5","key":"2026082211091836100_cit15","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/S0092-8674(03)00394-5","article-title":"Nanog:\nA New Recruit to the Embryonic Stem Cell Orchestra","volume":"113","author":"Cavaleri","year":"2003","journal-title":"Cell"},{"issue":"11","key":"2026082211091836100_cit16","doi-asserted-by":"publisher","first-page":"2281","DOI":"10.1038\/nprot.2013.143","article-title":"Genome engineering using the CRISPR-Cas9\nsystem","volume":"8","author":"Ran","year":"2013","journal-title":"Nat. Protoc."},{"key":"2026082211091836100_cit17","doi-asserted-by":"publisher","first-page":"793","DOI":"10.3390\/cells10040793","article-title":"Comparative Neurodevelopment\nEffects of Bisphenol A\nand Bisphenol F on Rat Fetal Neural Stem Cell Models","volume":"10","author":"Gill","year":"2021","journal-title":"Cells"},{"key":"2026082211091836100_cit18","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1692333","article-title":"Endocrine-disrupting\neffects of environmental BPS and PFOS on human brain organoid development","volume":"16","author":"Di Credico","year":"2025","journal-title":"Front. Endocrinol."},{"key":"2026082211091836100_cit19","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2024.115039","article-title":"Development of a TBXT-EGFP\niPS cell model for screening\nthe early developmental toxicity of typical environmental pollutants","volume":"193","author":"Zhao","year":"2024","journal-title":"Food Chem. Toxicol."},{"issue":"19","key":"2026082211091836100_cit20","doi-asserted-by":"publisher","first-page":"8215","DOI":"10.1021\/acs.est.3c10758","article-title":"Assessment\nand Comparison of Early Developmental Toxicity of Six Per- and Polyfluoroalkyl\nSubstances with Human Embryonic Stem Cell Models","volume":"58","author":"Zhao","year":"2024","journal-title":"Environ. Sci. 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Genet."},{"key":"2026082211091836100_cit23","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2025.108857","article-title":"The biological effects\nof bisphenol AF in reproduction and development: What do we know so\nfar?","volume":"132","author":"Alexander","year":"2025","journal-title":"Reproductive Toxicology"},{"key":"2026082211091836100_cit24","doi-asserted-by":"publisher","DOI":"10.1016\/j.chemosphere.2023.140815","article-title":"Occurrence\nand toxicity mechanisms of perfluorobutanoic\nacid (PFBA) and perfluorobutane sulfonic acid (PFBS) in fish","volume":"349","author":"Ivantsova","year":"2024","journal-title":"Chemosphere"},{"key":"2026082211091836100_cit25","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2020.110690","article-title":"PFAS and cancer, a\nscoping review of the epidemiologic\nevidence","volume":"194","author":"Steenland","year":"2021","journal-title":"Environmental Research"},{"key":"2026082211091836100_cit26","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.scitotenv.2017.09.194","article-title":"Occurrence of bisphenol\nS in the environment and implications for human exposure: A short\nreview","volume":"615","author":"Wu","year":"2018","journal-title":"Science of The Total Environment"},{"issue":"1","key":"2026082211091836100_cit27","first-page":"102","article-title":"Penicillin-Streptomycin\nInduces Mouse Embryonic Stemcells Differentiation into Cardiomyocytes\nThrough MAPK Signal Pathway","volume":"2","author":"Su","year":"2023","journal-title":"J. Stem Cells Clin.\nPract."}],"container-title":["Environment &amp; Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/envhealth.5c00797","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/ehnea2\/article-pdf\/4\/8\/1732\/66264155\/envhealth.5c00797.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/ehnea2\/article-pdf\/4\/8\/1732\/66264155\/envhealth.5c00797.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T15:10:14Z","timestamp":1787411414000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/ehnea2\/article\/4\/8\/1732\/5233020\/A-NANOG-EGFP-iPSC-Based-Reporter-Platform-for-High"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,1]]},"references-count":27,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,4,1]]},"published-print":{"date-parts":[[2026,8,21]]}},"URL":"https:\/\/doi.org\/10.1021\/envhealth.5c00797","relation":{},"ISSN":["2833-8278"],"issn-type":[{"value":"2833-8278","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,1]]}}}