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dc.contributor.authorXu, Cheng
dc.contributor.authorShen, Wei-Bin
dc.contributor.authorReece, E Albert
dc.contributor.authorHasuwa, Hidetoshi
dc.contributor.authorHarman, Christopher
dc.contributor.authorKaushal, Sunjay
dc.contributor.authorYang, Peixin
dc.date.accessioned2021-07-06T13:59:32Z
dc.date.available2021-07-06T13:59:32Z
dc.date.issued2021-06-30
dc.identifier.urihttp://hdl.handle.net/10713/16134
dc.description.abstractNeural tube defects (NTDs) are the second most common structural birth defect. Senescence, a state of permanent cell cycle arrest, occurs only after neural tube closure. Maternal diabetes-induced NTDs are severe diabetic complications that lead to infant mortality or lifelong morbidity and may be linked to premature senescence. Here, we report that premature senescence occurs in the mouse neuroepithelium and disrupts neurulation, leading to NTDs in diabetic pregnancy. Premature senescence and NTDs were abolished by knockout of the transcription factor Foxo3a, the miR-200c gene, and the cell cycle inhibitors p21 and p27; transgenic expression of the dominant-negative FoxO3a mutant; or the senomorphic rapamycin. Double transgenic expression of p21 and p27 mimicked maternal diabetes in inducing premature neuroepithelium senescence and NTDs. These findings integrate transcription- and epigenome-regulated miRNAs and cell cycle regulators in premature neuroepithelium senescence and provide a mechanistic basis for targeting premature senescence and NTDs using senomorphics.en_US
dc.description.urihttps://doi.org/10.1126/sciadv.abf5089en_US
dc.language.isoenen_US
dc.publisherAmerican Association for the Advancement of Scienceen_US
dc.relation.ispartofScience Advancesen_US
dc.rightsCopyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).en_US
dc.subject.meshCellular Senescenceen_US
dc.subject.meshNeural Tube Defectsen_US
dc.subject.meshPregnancy in Diabeticsen_US
dc.titleMaternal diabetes induces senescence and neural tube defects sensitive to the senomorphic rapamycinen_US
dc.typeArticleen_US
dc.identifier.doi10.1126/sciadv.abf5089
dc.identifier.pmid34193422
dc.source.volume7
dc.source.issue27
dc.source.countryUnited States


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