Biology subjects

Weckmann, M.

Publications and source records attributed to Weckmann, M..

3 recordsLinked to original sources

bioRxiv2026

A repair-associated bronchial epithelial differentiation trajectory through KRT14+ basal and hillock-like cells drives airway inflammation and remodelling in childhood-onset asthma

The bronchial epithelium in asthma is vulnerable to damage and has impaired barrier function, but the mechanisms by which it contributes to airway inflammation and remodelling remain unclear. Here, we dissect these epithelial and immunological disease mechanisms by establishing a comprehensive single cell atlas of the bronchial wall from 21 patients with childhood-onset asthma and 25 matched healthy controls. We identify a novel asthma-associated non-canonical epithelial differentiation trajectory in which a repair-associated KLF4+ basal cell subset differentiates into KRT13+ hillock-like cells through a proliferative KRT14+ intermediate. In vitro cultured matched primary bronchial epithelial cells show that this trajectory is retained in absence of exogenous factors. We find that IL-13 induces hillock-like cell differentiation into CEACAM5hi goblet cells, driving goblet cell metaplasia. Repair-associated basal cells and transitioning CEACAM5hi hillock-like cells strongly contribute to airway inflammation and remodelling. In turn, dendritic cells and mast cells promote a state of highly active epithelial differentiation, which shows increased multiciliated cell fate decisions, in concordance with an increase in multiciliated cell death observed in asthma. Proportions of the epithelial cells of the non-canonical differentiation trajectory are associated with clinical outcomes such as disease severity, FeNO, and small airway function.

immunology↗

bioRxiv2026

Fragmented gut-airway microbial networks and airway Moraxella clusters in preschool wheeze

Early-life wheezing in children has been associated with microbial alterations along the gut-airway axis, yet studies simultaneously investigating bacterial communities in both compartments remain scarce. The aim of this cross-sectional exploratory pilot study (n=25) was to characterize and compare nasal and stool bacterial communities in preschool children aged 1-4 years with recurrent wheezing and healthy controls using 16S rRNA gene metabarcoding. Across participants, nasal and stool bacteriomes were highly individualized and taxonomically diverse. Overall richness, evenness, and community composition did not differ significantly between healthy children and wheezers in either compartment. However, wheezers displayed markedly higher within-group variability, particularly in nasal communities. Stratification based on microbiome similarity to healthy samples revealed increased Moraxella and reduced commensal genera including Prevotella spp. and Veillonella, along with lower richness and evenness (all p<0.001) in nasal samples with divergent bacterial communities. Stool alterations were more subtle but included trends toward reduced Bacteroides, Faecalibacterium, and Alistipes in wheezers more divergent from healthy controls. Community assembly in both compartments was largely governed by stochastic processes but accompanied by less complex and more fragmented bacterial interaction networks in wheezing children. Cross-compartment correlations were also altered, most prominently involving stool Lactococcus showing stronger and more numerous correlations with nasal taxa in wheezers than in healthy controls. Divergent wheezers exhibited distinct modular network structure and cross-compartment profiles, consistent with a differentiated microbial organization. Together, these findings suggest compartment-specific differences in microbial interaction patterns across the gut-airway axis in early-life wheezing, despite limited differences in overall community diversity. Take home messagePreschool wheezers showed fragmented gut-airway microbial networks and Moraxella-associated airway community stratification despite limited differences in overall diversity.

microbiology↗

bioRxiv2024

scRNA-seq reveals persistent aberrant differentiation of nasal epithelium driven by TNFα and TGFβ in post-COVID syndrome

Post-COVID syndrome (PCS) currently affects approximately 3-17% of people following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and has the potential to become a significant global health burden. PCS presents with various symptoms, and methods for improved PCS assessment are presently developed to guide therapy. Nevertheless, there are few mechanistic insights and treatment options. Here, we performed single-cell RNA transcriptomics on nasal biopsies from 33 patients suffering from PCS with mild, moderate, or severe symptoms. We identified 17 different cell clusters representing 12 unique cell populations, including all major epithelial cell types of the conducting airways and basal, secretory, and ciliated cells. Severe PCS was associated with decreased numbers of ciliated cells and the presence of immune cells. Ensuing inflammatory signaling upregulated TGF{beta} and induced an epithelial-mesenchymal transition, which led to the high abundance of basal cells and a mis-stratified epithelium. We confirmed the results in vitro using an air-liquid interface culture and validated TNF as the causal inflammatory cytokine. In summary, our results show that one mechanism for sustained PCS is not through continued viral load, but through the presence of immune cells in nasal tissue leading to impaired mucosal barrier function and repeated infections. These findings could be further explored as a therapeutic option akin to other chronic inflammatory diseases by inhibiting the TNF-TGF{beta} axis, restoring the nasal epithelium, and reducing respiratory tract-related infections.

genomics↗