{
  "abstract": "DNA methylation is a fundamental epigenetic modification that regulates gene expression, cellular identity, and disease-associated regulatory programs. However, high-throughput single-cell DNA methylation technologies have been limited by DNA degradation, low CpG recovery, and the poor scalability of bisulfite-based methods. Here, we present scEM-seq, a droplet-based single-cell enzymatic methylome sequencing method that integrates barcode ligation within a single emulsification step, followed by postemulsion cytosine-to-uracil conversion. This design substantially reduces DNA loss and enables robust profiling of tens of thousands of single cells per experiment. scEM-seq generates high-quality single-cell methylomes with moderately improved CpG coverage and balanced read utilization compared with other droplet-based microfluidic methods. Applied to peripheral blood mononuclear cells, scEM-seq accurately resolves major immune lineages, and in prostate cancer tissues, it reveals diverse malignant cell states and patient-specific epigenetic and copy number architectures. scEM-seq enables scalable single-cell dissection of epigenetic heterogeneity across diverse biological and disease contexts, broadening the scope of DNA methylation-based studies into cellular regulation and disease.",
  "abstract_shown": true,
  "affiliations": [
    "China National Center for Bioinformation, Beijing 100101, China.",
    "Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 100101, China.",
    "University of Chinese Academy of Sciences, Beijing 100049, China.",
    "Department of Pharmacy, Peking University First Hospital, Beijing 100034, China.",
    "School of Medicine, Nankai University, Tianjin 30071, China.",
    "Department of Urology, Chinese PLA General Hospital, Beijing 100039, China.",
    "SeekGene BioSciences Co. Ltd., Beijing 102206, China.",
    "Department of Urology, Peking University First Hospital, Institution of Urology, Peking University, Beijing 100034, China.",
    "Beijing Key Laboratory of Urogenital Diseases (Male) Molecular Diagnosis and Treatment Center, National Urological Cancer Center, Beijing 100034, China."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Gaojie Li",
      "orcid": "0009-0003-3869-1847"
    },
    {
      "affs": [
        0,
        1,
        2,
        3
      ],
      "name": "Yang Yang",
      "orcid": "0009-0005-1207-3383"
    },
    {
      "affs": [
        4,
        5
      ],
      "name": "Zhuoran Li",
      "orcid": "0009-0001-7367-7835"
    },
    {
      "affs": [
        5
      ],
      "name": "Qi Wang",
      "orcid": "0000-0002-1973-8510"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Ying Wang",
      "orcid": "0009-0009-1048-054X"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Bin Guo",
      "orcid": "0000-0002-0748-7179"
    },
    {
      "affs": [
        5
      ],
      "name": "Kunmeng Yang",
      "orcid": "0009-0002-8582-5150"
    },
    {
      "affs": [
        6
      ],
      "name": "Ming Tan",
      "orcid": "0009-0009-2424-2884"
    },
    {
      "affs": [
        6
      ],
      "name": "Jinwei Li"
    },
    {
      "affs": [
        6
      ],
      "name": "Jiacheng Sun",
      "orcid": "0009-0008-4216-0770"
    },
    {
      "affs": [
        6
      ],
      "name": "Guangxin Zhang",
      "orcid": "0000-0002-1791-3119"
    },
    {
      "affs": [
        7,
        8
      ],
      "name": "Shengwei Xiong",
      "orcid": "0000-0003-4885-899X"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Mei Zhang",
      "orcid": "0009-0001-2975-5488"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Zhihua Zhang",
      "orcid": "0000-0002-7706-9247"
    },
    {
      "affs": [
        6
      ],
      "name": "Yingying Xie",
      "orcid": "0009-0005-6631-2175"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Yue Shi",
      "orcid": "0000-0001-5121-2116"
    },
    {
      "affs": [
        5
      ],
      "name": "Xin Ma",
      "orcid": "0000-0002-7316-1468"
    },
    {
      "affs": [
        5
      ],
      "name": "Weimin Ci",
      "orcid": "0000-0002-4111-5360"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/ez73m9jascmtj.bib",
  "cited_by": 0,
  "doi": "10.1126/sciadv.aef2844",
  "fulltext_url": "https://europepmc.org/articles/PMC13693690",
  "id": "ez73m9jascmtj",
  "issns": [
    "2375-2548"
  ],
  "landing_url": "https://www.science.org/doi/10.1126/sciadv.aef2844",
  "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": "W7223416941",
  "pdf_url": "https://europepmc.org/articles/PMC13693690?pdf=render",
  "pmcid": "PMC13693690",
  "pmid": "42913020",
  "published": "2026-10-23",
  "publisher": "American Association for the Advancement of Science (AAAS)",
  "ris": "https://research.draconitic.com/paper/ez73m9jascmtj.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:41Z",
      "native_id": "10.1126/sciadv.aef2844",
      "source": "crossref",
      "url": "https://www.science.org/doi/10.1126/sciadv.aef2844"
    },
    {
      "first_seen": "2026-10-30T12:20:03Z",
      "native_id": "MED:42913020",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42913020"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Epigenetics and DNA Methylation",
      "subfield": "molecular-biology"
    }
  ],
  "title": "High-throughput droplet-based enzymatic DNA methylome profiling enables single-cell resolution of epigenetic heterogeneity",
  "title_text": "High-throughput droplet-based enzymatic DNA methylome profiling enables single-cell resolution of epigenetic heterogeneity",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:03Z",
  "url": "https://research.draconitic.com/paper/ez73m9jascmtj",
  "venue": "Science Advances",
  "versions": []
}