{
  "abstract": "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.",
  "abstract_shown": true,
  "affiliations": [
    "Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signal Transduction and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China.",
    "Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.",
    "Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopaedic Department of Tongji Hospital, School of Life Sciences and Technology, Tongji University, Shanghai 200065, China.",
    "Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 201204, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1
      ],
      "name": "Shanru Yi",
      "orcid": "0009-0009-1255-4012"
    },
    {
      "affs": [
        2
      ],
      "name": "Jing Xiao",
      "orcid": "0000-0003-4419-9114"
    },
    {
      "affs": [
        3
      ],
      "name": "Ruixue Wang",
      "orcid": "0009-0002-6568-0521"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mengting Wang",
      "orcid": "0009-0009-5658-1178"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Chunyan Le"
    },
    {
      "affs": [
        2
      ],
      "name": "Guang Yang",
      "orcid": "0000-0002-1910-9271"
    },
    {
      "affs": [
        2
      ],
      "name": "Shanshan Yi",
      "orcid": "0000-0003-3716-9566"
    },
    {
      "affs": [
        2
      ],
      "name": "Wenju Liu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Hong Wang"
    },
    {
      "affs": [
        3
      ],
      "name": "Xiaocui Li"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Xiaoyu Liu",
      "orcid": "0000-0001-6622-9316"
    },
    {
      "affs": [
        3
      ],
      "name": "Kai Wang",
      "orcid": "0000-0003-2298-4816"
    },
    {
      "affs": [
        2
      ],
      "name": "Cizhong Jiang",
      "orcid": "0000-0001-5406-2360"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Shaorong Gao",
      "orcid": "0000-0003-1041-3928"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Jiayu Chen",
      "orcid": "0000-0003-4755-8901"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/81ag2qypnv120.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aee0560",
  "fulltext_url": "https://europepmc.org/articles/PMC13693670",
  "id": "81ag2qypnv120",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aee0560",
  "language": "eng",
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Epigenetics and DNA Methylation"
    ]
  ],
  "openalex": "W7223413885",
  "pdf_url": "https://europepmc.org/articles/PMC13693670?pdf=render",
  "pmcid": "PMC13693670",
  "pmid": "42912993",
  "published": "2026-10-23",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/81ag2qypnv120.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aee0560",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aee0560"
    },
    {
      "first_seen": "2026-10-30T12:20:03Z",
      "native_id": "MED:42912993",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42912993"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Epigenetics and DNA Methylation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Lineage-specific and gestational age–dependent DNA methylation programming orchestrates human placental development",
  "title_text": "Lineage-specific and gestational age–dependent DNA methylation programming orchestrates human placental development",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:03Z",
  "url": "https://research.draconitic.com/paper/81ag2qypnv120",
  "venue": "Science Advances",
  "versions": []
}