{
  "abstract": "Understanding the molecular underpinnings of stem cell differentiation is pivotal for generating appropriate cell types in cell-based therapies. Differentiation of human pluripotent stem cells (PSC) into corneal limbal stem cells offers a promising avenue to regenerate the corneal epithelium. However, current differentiation strategies remain inconsistent in efficiency and yield heterogeneous cell populations that incompletely recapitulate the regenerative properties of donor-derived limbal stem cells. Here, we mapped the molecular landscape of cell states throughout the differentiation process. First, we construct PSC differentiation paths from single-cell RNA sequencing (scRNA-seq) data using the computational framework of optimal transport, identifying on- and off-track cell states toward the limbal stem cell state. Single cell Assay for Transposase-Accessible Chromatin sequencing (scATAC-seq) was performed to profile accessible genomic regions, and subsequently integrated with scRNA-seq data through gene regulatory network analysis to identify key drivers governing the diverse cell states. We showed that genomic enhancers play a major role in cell state determinations. Through this single-cell multi-modal approach, we identified potential transcription factors driving limbal epithelial lineage specification and off-track cell populations. Our findings provide a framework for rational optimization of PSC-derived limbal stem cell generation to advance the development of corneal cell therapies.",
  "abstract_shown": true,
  "affiliations": [
    "Radboud University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "name": "J. A. Arts"
    },
    {
      "name": "D. Lima Cunha"
    },
    {
      "name": "S. Harjuntausta"
    },
    {
      "name": "M. Vattulainen"
    },
    {
      "name": "J. G. Smits"
    },
    {
      "name": "I. Bonthuis"
    },
    {
      "name": "D. Fragoso Bento"
    },
    {
      "name": "F. Bocci"
    },
    {
      "name": "H. Skottman"
    },
    {
      "affs": [
        0
      ],
      "name": "H. Zhou"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aeparhcckh34t.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.16.751974",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751974v1.full",
  "id": "aeparhcckh34t",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751974v1",
  "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",
      "molecular biology"
    ],
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W7213495186",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751974v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-16",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/aeparhcckh34t.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:22:55Z",
      "native_id": "10.64898/2026.09.16.751974",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.16.751974v2"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "biorxiv:molecular biology",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Mapping heterogeneity drivers in human PSC-derived limbal stem cell differentiation through single-cell multi-modal analysis",
  "title_text": "Mapping heterogeneity drivers in human PSC-derived limbal stem cell differentiation through single-cell multi-modal analysis",
  "type": "preprint",
  "updated_at": "2026-10-30T12:24:08Z",
  "url": "https://research.draconitic.com/paper/aeparhcckh34t",
  "venue": "bioRxiv",
  "versions": []
}