Clade B serpins promote direct basal-to-goblet cell differentiation in airways of patients with chronic obstructive pulmonary disease
- 1Vanderbilt University Medical Center
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.
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BibTeX
@misc{tufenkjian2026clade,
title = {{Clade B serpins promote direct basal-to-goblet cell differentiation in airways of patients with chronic obstructive pulmonary disease}},
author = {T. S. Tufenkjian and J. B. Blackburn and D. Nichols and A. Vasquez and C. Shaver and L. Ware and T. S. Blackwell and B. W. Richmond},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.753278},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.753278v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Clade B serpins promote direct basal-to-goblet cell differentiation in airways of patients with chronic obstructive pulmonary disease
AU - T. S. Tufenkjian
AU - J. B. Blackburn
AU - D. Nichols
AU - A. Vasquez
AU - C. Shaver
AU - L. Ware
AU - T. S. Blackwell
AU - B. W. Richmond
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.753278
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.753278v1
AB - 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.
ER -