Biology subjects

Fierville, M.

Publications and source records attributed to Fierville, M..

3 recordsLinked to original sources

bioRxiv2026

A distinct signature of interferon-stimulated genes linked to cross-protection against secondary viral infections in primary bronchial epithelial cells

Respiratory viral infections, such as those caused by rhinovirus, adenovirus, influenza, respiratory syncytial virus (RSV), and SARS-CoV-2, represent a major global health challenge. Despite extensive research, effective and specific antiviral treatments for these infections are still lacking, with patient care often limited to symptomatic relief. The SARS-CoV-2 pandemic, alongside the emergence of avian flu H1N1 and Nipah virus, has underscored the critical role of the respiratory tract as a critical viral target. Respiratory viral infections exhibit marked variability in infectivity and disease severity across different age groups. Epidemiological and cell-based evidence highlights distinct impacts on pediatric and adult populations. For instance, the COVID-19 disproportionately affected the elderly, while viruses like rhinovirus and adenovirus often cause severe morbidity in children. Additionally, clinical studies indicate that a primary respiratory infection can provide transient protection against subsequent infections by the same or different respiratory viruses. In this study, we utilized a differentiated bronchial epithelial (BE) model derived from pediatric and adult donors to assess age-dependent differences under resting conditions and during viral infections. We investigated how donor age influences infection susceptibility and viral spread within the BE, focusing on the transcriptional response to rhinovirus types A and C, and adenovirus type 5. Importantly, we demonstrate that prior viral infection confers protection against subsequent infections, regardless of donor age or the initial virus type. This cross-protection is driven by interferon signaling, leading to the expression of a narrow and specific set of interferon-stimulated genes (ISGs) in both infected and bystander cells. Notably, IFI44L shows the strongest correlation with the level of cross protection and that its overexpression alone significantly reduces viral infection of BE. These findings suggest a distinctive, interferon-driven innate immune response profile in the BE, offering critical insights for the development of new therapeutic strategies against respiratory viral infections.

microbiology↗

bioRxiv2024

scMusketeers: Addressing imbalanced cell type annotation and batch effect reduction with a modular autoencoder

The growing number of single-cell gene expression atlases available offers a conceptual framework for improving our understanding of physio-pathological processes. To take full advantage of this revolution, data integration and cell annotation strategies need to be improved, in particular to better detect rare cell types and by better controlling batch effects in experiments. scMusketeers is a deep learning model that optimises the representation of latent data and solves both challenges. scMusketeers features three modules: (1) an autoencoder for noise and dimensionality reductions; (2) a focal loss classifier to enhance rare cell type predictions; and (3) an adversarial domain adaptation (DANN) module for batch effect correction. Benchmarking against state-of-the-art tools, including the UCE foundation model, showed that scMusketeers performs on par or better, particularly in identifying rare cell types. It also allows to transfer cell labels from single-cell RNA sequencing to spatial transcriptomics. With its modular and adaptable design, scMusketeers offers a versatile framework that can be generalized to other large-scale biological projects requiring deep learning approaches, establishing itself as a valuable tool for single-cell data integration and analysis.

bioinformatics↗

bioRxiv2024

Cell culture differentiation and proliferation conditions influence the in vitro regeneration of the human airway epithelium

The human airway mucociliary epithelium can be recapitulated in vitro using primary cells cultured in an Air-Liquid Interface (ALI), a reliable surrogate to perform pathophysiological studies. As tremendous variations exist between media used for ALI-cultured human airway epithelial cells, our study aimed to evaluate the impact of several media (BEGMTM, PneumaCultTM, "Half&Half" and "Clancy") on cell type distribution using single-cell RNA sequencing and imaging. Our work revealed the impact of these media on cell composition, gene expression profile, cell signaling and epithelial morphology. We found higher proportions of multiciliated cells in PneumaCultTM-ALI and Half&Half, stronger EGF signaling from basal cells in BEGMTM-ALI, differential expression of the SARS-CoV-2 entry factor ACE2, and distinct secretome transcripts depending on media used. We also established that proliferation in PneumaCultTM-Ex Plus favored secretory cell fate, showing the key influence of proliferation media on late differentiation epithelial characteristics. Altogether, our data offer a comprehensive repertoire for evaluating the effects of culture conditions on airway epithelial differentiation and will help to choose the most relevant medium according to the processes to be investigated such as cilia, mucus biology or viral infection. We detail useful parameters that should be explored to document airway epithelial cell fate and morphology.

cell biology↗