{
  "abstract": "Decades of investigation have made the choice between CD4 and CD8 T cell lineages in the thymus a key paradigm for mammalian cell commitment and differentiation, yet how transcriptional diversification is coordinated with 3D genome organisation remains largely unexplored. Here, using single-molecule transcript quantification and region capture Pico-C (RCPC), we resolve distinct transcriptional and spatial chromatin dynamics at the lineage-defining loci Cd4 and Cd8. We find early Cd4/Cd8 transcriptional divergence driven by MHC-dependent bias in Cd8a transcript copy number, which unfolds gradually across both CCR7- and CCR7+ differentiation stages. Unexpectedly, Cd4 and Cd8 loci show fundamentally different spatial contact dynamics: transiently reduced mesoscale (10-100kb) contacts at Cd8 provide a permissive chromatin environment throughout the transcriptional diversification process. By contrast, Cd4 undergoes switch-like contact changes limited to the microscale (1kb) late in differentiation, associated with lineage stabilization by ThPOK and/or RUNX3. These results place distinct, locus-specific chromatin environments at the centre of transcriptional diversification during T cell lineage choice.",
  "abstract_shown": true,
  "affiliations": [
    "MRC Laboratory of Medical Sciences, Imperial College London"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "I. Patrascan"
    },
    {
      "name": "J. W. King"
    },
    {
      "name": "N. Maziak"
    },
    {
      "name": "R. M. Crossley"
    },
    {
      "name": "S. Johnson"
    },
    {
      "name": "A. Ceccarelli"
    },
    {
      "name": "I. McFarlane"
    },
    {
      "name": "Y. Guo"
    },
    {
      "name": "M. M. Karimi"
    },
    {
      "name": "A. G. Fisher"
    },
    {
      "name": "R. E. Baker"
    },
    {
      "name": "J. M. Vaquerizas"
    },
    {
      "affs": [
        0
      ],
      "name": "M. Merkenschlager"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/e7h4pxfn9tvaw.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.26.761611",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761611v1.full",
  "id": "e7h4pxfn9tvaw",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761611v1",
  "language": null,
  "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": [
    [
      "biorxiv",
      "genetics"
    ],
    [
      "openalex",
      "1312|Genomics and Chromatin Dynamics"
    ]
  ],
  "openalex": "W7223861155",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761611v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-26",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/e7h4pxfn9tvaw.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:29:51Z",
      "native_id": "10.64898/2026.10.26.761611",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.26.761611v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genetics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Locus-specific spatial and transcriptional dynamics direct T cell lineage choice in the thymus",
  "title_text": "Locus-specific spatial and transcriptional dynamics direct T cell lineage choice in the thymus",
  "type": "preprint",
  "updated_at": "2026-10-30T12:29:51Z",
  "url": "https://research.draconitic.com/paper/e7h4pxfn9tvaw",
  "venue": "bioRxiv",
  "versions": []
}