{
  "abstract": "Goblet cell hyperplasia (GCH) is a hallmark of chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality. We investigated the cellular and molecular origins of GCH in COPD using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and in vitro models. We identified \"basal-to-goblet transitional cells\" (BGTC) which are transcriptionally and physically located between basal and goblet cells and are characterized by expression of clade B serpins. In vitro studies indicate that inflammatory cytokines, including IL-1{beta}, stimulate basal-to-goblet differentiation through a SERPINB3/4+ intermediate and SERPINB3 overexpression induces differentiation of airway basal cells into IL1B-producing inflammatory goblet cells. In addition, we identified a subset of SERPINB4+ \"goblet-variant basal cells\" from lungs of COPD patients that express goblet cell and inflammatory genes ex vivo. Together, these results indicate clade B serpins contribute to altered epithelial differentiation and inflammatory signaling in COPD and support therapeutic targeting of clade B serpins to reduce GCH.",
  "abstract_shown": true,
  "affiliations": [
    "Vanderbilt University Medical Center"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "T. S. Tufenkjian"
    },
    {
      "name": "J. B. Blackburn"
    },
    {
      "name": "D. Nichols"
    },
    {
      "name": "A. Vasquez"
    },
    {
      "name": "C. Shaver"
    },
    {
      "name": "L. Ware"
    },
    {
      "name": "T. S. Blackwell"
    },
    {
      "affs": [
        0
      ],
      "name": "B. W. Richmond"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/42j1qrb0gdzdg.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.21.753278",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753278v1.full",
  "id": "42j1qrb0gdzdg",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753278v1",
  "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",
      "cell biology"
    ],
    [
      "openalex",
      "2740|Chronic Obstructive Pulmonary Disease (COPD) Research"
    ]
  ],
  "openalex": "W7214036355",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753278v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-21",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/42j1qrb0gdzdg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:23:58Z",
      "native_id": "10.64898/2026.09.21.753278",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.21.753278v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:cell biology",
      "subfield": "cell-biology"
    }
  ],
  "title": "Clade B serpins promote direct basal-to-goblet cell differentiation in airways of patients with chronic obstructive pulmonary disease",
  "title_text": "Clade B serpins promote direct basal-to-goblet cell differentiation in airways of patients with chronic obstructive pulmonary disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:23:58Z",
  "url": "https://research.draconitic.com/paper/42j1qrb0gdzdg",
  "venue": "bioRxiv",
  "versions": []
}