{
  "abstract": "Human fetal haematopoiesis requires developmental potential to be encoded before lineage identity becomes transcriptionally apparent, but whether three-dimensional genome architecture provides such information is unknown. Here we develop ChromE-seq, a scalable single-cell assay that jointly profiles chromatin conformation and transcription, and integrate it with chromatin accessibility and DNA methylation to generate a multimodal atlas of ~400,000 haematopoietic cells from disomic and trisomy 21 (T21) human fetal liver. Chromatin contacts frequently preceded lineage-specific transcription or persisted after transcription declined, revealing 3D chromatin priming and memory. Unexpectedly, B-lineage and erythroid differentiation followed opposing architectural trajectories, with progressive loss and gain of chromatin connectivity, respectively. T21 disproportionately disrupted B-lineage architecture, redistributed interactions towards shorter genomic distances and weakened an EBF1-centred regulatory circuit. Deletion of a T21-sensitive EBF1 loop anchor reproduced the CLP-to-B-progenitor bottleneck observed in T21. These findings establish 3D genome architecture as an organizing layer of human fetal haematopoiesis that links developmental potential with lineage-specific vulnerability to genomic perturbation.",
  "abstract_shown": true,
  "affiliations": [
    "Icahn School of Medicine at Mount Sinai"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "Z. Liao"
    },
    {
      "name": "M. Zhang"
    },
    {
      "name": "B. Y. Soong"
    },
    {
      "name": "B. Zhu"
    },
    {
      "name": "L. L. Boshans"
    },
    {
      "name": "K. Wang"
    },
    {
      "name": "M. Quijada-Alamo"
    },
    {
      "name": "I. Osakwe"
    },
    {
      "name": "Z. Wang"
    },
    {
      "name": "P. Fiore"
    },
    {
      "name": "D. Hasson"
    },
    {
      "name": "E. Wagenblast"
    },
    {
      "affs": [
        0
      ],
      "name": "S. Ma"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9kppaeenae62m.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.07.757425",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757425v1.full",
  "id": "9kppaeenae62m",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757425v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7221436937",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757425v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9kppaeenae62m.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:27:05Z",
      "native_id": "10.64898/2026.10.07.757425",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757425v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Disrupted chromatin architecture blocks B lymphopoiesis in Down syndrome",
  "title_text": "Disrupted chromatin architecture blocks B lymphopoiesis in Down syndrome",
  "type": "preprint",
  "updated_at": "2026-10-30T12:27:05Z",
  "url": "https://research.draconitic.com/paper/9kppaeenae62m",
  "venue": "bioRxiv",
  "versions": []
}