Clade B serpins promote direct basal-to-goblet cell differentiation in airways of patients with chronic obstructive pulmonary disease
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…
Chronic obstructive pulmonary disease (COPD) is characterized by goblet cell hyperplasia (GCH), a condition that leads to significant morbidity and mortality. Researchers employed single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and in vitro models to investigate the cellular and molecular origins of GCH in COPD patients. They identified basal-to-goblet transitional cells (BGTC), which are located between basal and goblet cells and are characterized by the expression of clade B serpins.
The in vitro studies revealed that inflammatory cytokines, such as IL-1β, stimulate basal-to-goblet differentiation via a SERPINB3/4+ intermediate. Moreover, SERPINB3 overexpression induces airway basal cells to transform into IL1B-producing inflammatory goblet cells. Furthermore, the researchers identified a subset of SERPINB4+ goblet-variant basal cells in the lungs of COPD patients, which express goblet cell and inflammatory genes in an ex vivo setting.
In conclusion, the findings suggest that clade B serpins play a role in altered epithelial differentiation and inflammatory signaling in COPD. The research supports the therapeutic targeting of clade B serpins as a potential strategy to reduce goblet cell hyperplasia in COPD patients.
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