{"id":383,"title":"Lineage-specific and gestational age-dependent DNA methylation programming orchestrates human placental development","title_zh":"人类胎盘发育的谱系特异性与孕龄依赖DNA甲基化编程","url":"https://pubmed.ncbi.nlm.nih.gov/42912993","doi":"10.1126/sciadv.aee0560","pmid":"42912993","journal":"Sci Adv","kind":"paper","lang":"en","published_at":"2026-10-23T00:00:00+00:00","fetched_at":"2026-11-08T03:44:12+00:00","authors":["Yi S","Xiao J","Wang R","Wang M","Le C","Yang G","Yi S","Liu W","Wang H","Li X","Liu X","Wang K","Jiang C","Gao S","Chen J"],"primary_topic":"endometrium","topics":[{"slug":"endometrium","score":6.0,"hits":["placenta","placental","trophoblast"]},{"slug":"repro-genetics","score":5.0,"hits":["dna methylation","methylome"]},{"slug":"ethics-policy","score":1.0,"hits":["regulation"]}],"topic_score":6.0,"preference_score":0.0,"preference_labels":[],"llm_score":84.0,"final_score":92.0,"score_dims":{"novelty":88,"rigor":87,"impact":82,"relevance":82,"translation":72},"recommend_reason":"提供跨孕龄单碱基分辨率胎盘甲基化图谱，将表观遗传编程与胎盘成熟、免疫稳态及早产联系起来，对理解植入后早期妊娠和ART相关胎盘风险有参考价值；但属于机制性研究，尚未直接转化为临床干预。","keywords":["人类胎盘","滋养层","DNA甲基化","单碱基图谱","DNMT1","早产"],"selected":1,"story_id":333,"llm_provider":"deepseek","llm_model":"deepseek-flash","llm_effort":"low","source_key":"pubmed-top-journals","source_name":"PubMed · CNS/大子刊/四大医学刊（生殖相关）","source_tier":1,"mention_count":1,"has_interpretation":false,"journal_key":"sci-adv","journal_tier":"cns-sub","journal_if":11.7,"is_mock":false,"summary_zh":"该研究构建了覆盖妊娠期的人胎盘滋养层单碱基分辨率DNA甲基化图谱，发现植入后即建立谱系特异性甲基化程序，并随孕龄累积，作为协调胎盘成熟与免疫稳态的发育屏障。整合组蛋白修饰与功能扰动揭示H3K27me3与DNA甲基化沉默促炎位点、重复序列由H3K9me3向DNA甲基化转换以维持基因组稳定；早产胎盘存在甲基化异常。人滋养层干细胞实验表明DNMT1维持甲基化组完整与自我更新，DNMT3家族对存活同等重要。","summary":"The human placenta is essential for pregnancy, yet the dynamic regulation of its DNA methylome during development remains poorly understood. To address this, we generated a single base-resolution DNA methylation atlas of human placental trophoblasts across gestation. We identified a lineage-specific methylation program established immediately after implantation, followed by gestational age-dependent methylation accumulation. This program acted as a developmental barrier that coordinated placental maturation and immune homeostasis. By integrating histone modifications and functional perturbations, we revealed a temporal dynamic between H3K27me3 and DNA methylation that silenced proinflammatory loci and a switch from H3K9me3 to DNA methylation at repeat elements to maintain genome stability. Aberrant methylation in preterm placentas underscored the physiological importance of methylation regulation. Using human trophoblast stem cells, we demonstrated that DNMT1 was critically required for maintaining trophoblast methylome integrity and self-renewal, while the DNMT3 family were equally essential for trophoblast survival. Overall, we established a placenta-specific epigenetic framework for human trophoblast development.","interpretation_basis":null,"fulltext_status":"ok","interpretation":null,"fulltext":{"available":true,"status":"ok","reason":"已取得 Europe PMC OA 全文","pmcid":"PMC13693670","license":"CC BY-NC","chars":29997,"source":"Europe PMC","fetched_at":"2026-11-08T03:59:50+00:00"}}