{
  "abstract": "The thymus enacts central tolerance through thymic (TECs), which present self-antigens to developing T cells self-reactive cells, preventing autoimmunity. Human TECs include populations that express lineage-committed programs corresponding to distinct peripheral tissues, yet how they acquire these programs and whether these TEC subpopulations are genetically related and conserved in mice remain unknown. Using matched single-cell gene-expression and chromatin-accessibility profiling of 126,687 human TECs, we identified 17 TEC subsets defined by their distinct expression profiles of 1,843 cell type restricted-antigens (CRAs) from 48 peripheral cell types. With a new phylogenetic reconstruction method, we show that lineage-committed TECs share a common ancestor, retain a thymus-specific mixed identity through co-expression of multiple CRA signatures, and are specified by coordinated activator and repressor regulons. We also identified a basement-membrane-collagen-rich state (BMC-TECs) with progenitor-like properties. Finally, mouse TECs shared the regulatory strategy but conserved few master transcription-factor drivers. This study mechanistically characterizes human TEC subpopulations and reveals the gene regulatory logic that leads to their distinct diversification and mixed identities in humans and mice.",
  "abstract_shown": true,
  "affiliations": [
    "Simons Center for Quantitative Biology, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 18,
  "authors": [
    {
      "name": "R. K. Prabakar"
    },
    {
      "name": "S. R. Chapin"
    },
    {
      "name": "Y. Lin"
    },
    {
      "name": "S. J. Staklinski"
    },
    {
      "name": "D. M. Netz"
    },
    {
      "name": "M. E. Lapine"
    },
    {
      "name": "D. Pruss"
    },
    {
      "name": "T. Cvetanovic"
    },
    {
      "name": "S. L. Carcy"
    },
    {
      "name": "J. Torres"
    },
    {
      "name": "A. Grosh"
    },
    {
      "name": "A. J. Kiedrowski"
    },
    {
      "name": "H. I. Pass"
    },
    {
      "name": "R. Mosca"
    },
    {
      "name": "C. Regan"
    },
    {
      "name": "J. Preall"
    },
    {
      "name": "A. Siepel"
    },
    {
      "affs": [
        0
      ],
      "name": "H. V. Meyer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/57rz0ejak5arb.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.29.762771",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762771v1.full",
  "id": "57rz0ejak5arb",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762771v1",
  "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",
      "immunology"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762771v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-29",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/57rz0ejak5arb.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T00:20:43Z",
      "native_id": "10.64898/2026.10.29.762771",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.29.762771v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:immunology",
      "subfield": "immunology"
    }
  ],
  "title": "Gene regulatory logic underlying the differentiation of mixed lineages in human thymic epithelial cells",
  "title_text": "Gene regulatory logic underlying the differentiation of mixed lineages in human thymic epithelial cells",
  "type": "preprint",
  "updated_at": "2026-11-04T00:21:14Z",
  "url": "https://research.draconitic.com/paper/57rz0ejak5arb",
  "venue": "bioRxiv",
  "versions": []
}