Biology subjects

Vanaudenaerde, B. M.

Publications and source records attributed to Vanaudenaerde, B. M..

3 recordsLinked to original sources

bioRxiv2025

Alveolar epithelial cell plasticity and injury memory in human pulmonary fibrosis

Acute and repetitive lung epithelial injury can lead to irreversible and even progressive pulmonary fibrosis; Idiopathic pulmonary fibrosis (IPF) is a fatal disease and quintessential example of this phenomenon. The composition of epithelial cells in human pulmonary fibrosis - irrespective of disease etiology - is marked by the presence of Aberrant Basaloid cells: an abnormal cell phenotype with pro-fibrotic and senescent features, localized to the surface of fibrotic lesions. Despite their relevance to human pulmonary fibrosis, the exotic molecular profile of Aberrant Basaloid cells has obscured their etiology, preventing insights into how or why these cells emerge with fibrosis. Here we identify cellular intermediaries between Aberrant Basaloid and normal alveolar epithelial cells in human IPF tissue. We track the emergence of Aberrant Basaloid cells from alveolar epithelial cells ex vivo and uncover a role for similar cells in epithelial regeneration under normal conditions. Lastly, we characterize the epigenetic changes that distinguish Aberrant Basaloid cells from their progenitors and identify hallmarks of AP-1 injury memory retention. This study elucidates the phenomenon of maladaptive epithelial plasticity and regeneration in pulmonary fibrosis and re-contextualizes therapeutic strategies for epithelial dysfunction.

cell biology↗

bioRxiv2023

A Multi-omic Analysis of the Human Lung Reveals Distinct Cell Specific Aging and Senescence Molecular Programs

Age is a major risk factor for lung disease. To understand the mechanisms underlying this association, we characterized the changing cellular, genomic, transcriptional, and epigenetic landscape of lung aging using bulk and single-cell RNAseq (scRNAseq) data. Our analysis revealed age-associated gene networks that reflected hallmarks of aging, including mitochondrial dysfunction, inflammation, and cellular senescence. Cell type deconvolution revealed age-associated changes in the cellular composition of the lung: decreased alveolar epithelial cells and increased fibroblasts and endothelial cells. In the alveolar microenvironment, aging is characterized by decreased AT2B cells and reduced surfactant production, a finding that was validated by scRNAseq and IHC. We showed that a previously reported senescence signature, SenMayo, captures cells expressing canonical senescence markers. SenMayo signature also identified cell-type specific senescence-associated co-expression modules that have distinct molecular functions, including ECM regulation, cell signaling, and damage response pathways. Analysis of somatic mutations showed that burden was highest in lymphocytes and endothelial cells and was associated with high expression of senescence signature. Finally, aging and senescence gene expression modules were associated with differentially methylated regions, with inflammatory markers such as IL1B, IL6R, and TNF being significantly regulated with age. Our findings provide new insights into the mechanisms underlying lung aging and may have implications for the development of interventions to prevent or treat age-related lung diseases.

genomics↗

bioRxiv2021

The memory of airway epithelium damage in smokers and COPD patients

RationaleChronic obstructive pulmonary disease (COPD) is a devastating and mostly irreversible lung disease. In COPD, the bronchial epithelium displays several structural and functional abnormalities affecting barrier integrity, cell polarity, and differentiation, as well as epithelial-to-mesenchymal transition and inflammation. Although COPD displays mostly irreversible changes, the (ir)reversible nature of epithelium pathology ex vivo remains poorly known and was the aim of this study. MethodsThe persistence of COPD epithelium abnormalities was addressed in long-term (10 weeks) primary cultures of air/liquid interface-reconstituted airway epithelium from non-smoker controls, smoker controls, and COPD patients. Barrier function, epithelial polarity, cell commitment, epithelial-to-mesenchymal transition and inflammation were assessed in vitro, and certain features were compared in situ to the native epithelium. The role of inflammation was explored by stimulating cultures with a cytokine mix consisting of TNF-, IL-6 and IL-1{beta}. Measurements and main resultsAlmost all epithelial defects (barrier dysfunction, impaired polarity, lineage abnormalities) observed in cells from smokers and COPD patients persisted in vitro up to week 10, except IL-8/CXCL-8 release and epithelial-to-mesenchymal transition which declined over time. Cell lineage and polarity impairments matched abnormalities observed in situ in the surgical samples from which the in vitro epithelium was derived. Cytokine treatment induced COPD-like changes and, in COPD cells, reactivated epithelial-to-mesenchymal transition. ConclusionsThe airway epithelium from smokers and COPD patients displays a memory of its native state and previous injuries by cigarette smoking, which is multidimensional and sustained for extended periods of time.

pathology↗