Biology subjects

Selman, M.

Publications and source records attributed to Selman, M..

4 recordsLinked to original sources

bioRxiv2026

Autophagy impairment by ATG4B deficiency reduces experimental hypersensitivity pneumonitis severity

Autophagy has been implicated in several lung diseases, either protecting tissues or driving pathology. Hypersensitivity pneumonitis (HP) is a complex inflammatory lung disease, and autophagy is heavily involved in regulating inflammation. The role of autophagy in HP remains unclear. The aim of our study was to understand the role of autophagy in HP pathogenesis. GFP-LC3 transgenic mice were exposed intranasally to Saccharopolyspora rectivirgula (SR) to induce HP and follow autophagy activation in the lung. Then, we take advantage of our Atg4b-deficient mouse model to assess how autophagy disruption impacts lung inflammation in response to SR antigen challenge. Increased autophagy activation was observed in epithelial and inflammatory cells after SR antigen exposure in GFP-LC3 transgenic lungs. GFP-LC3 puncta colocalized with ATG4B and ATG5 in epithelial and inflammatory cells after antigen exposure. Autophagy impairment limits the inflammatory response after SR antigen exposure in the lungs from the Atg4b-deficient mice when compared to WT mice. To evaluate whether lipopolysaccharide (LPS) exacerbates the inflammatory response in the Atg4b-deficient, a SR+LPS combined treatment was developed and we discovered that LPS aggravates the SR-induced HP in WT but not in Atg4b-deficient mice. Reduced HP severity in Atg4b-deficient mice was associated with decreased expression of NFkB, CCL1, CCL25, CXCL1, TNFR1, IL-13, and IL-17A, diminished CD4+ T cell recruitment and expansion, reduced M2-like macrophages, and decreased granuloma and iBALT development. Our findings highlight autophagy as a critical driver in HP pathogenesis and as a potetial target for novel theraphy development.

immunology↗

bioRxiv2026

Lung progenitors exhaustion in response to microenvironment stress during aging

Progenitor cells in aged tissues undergo changes in their microenvironment that may impact their functionality during regeneration. Despite recent advances in understanding the role of adult lung progenitors, the impact of aging on these cells remains unclear. To analyze aging modifications, we used aged wild-type mice of 18-24 months old, and Zmpste24-/- deficient mice, which exhibit an accelerated aging phenotype. A three-dimensional organoid culture system was employed to assess the lung regeneration capacity. Additionally, mouse epithelial cells and fibroblasts were isolated and characterized with senescence and autophagy markers. Our findings revealed that lung epithelial cells from aged mice and Zmpste24-/- mice hold their regeneration capacity, maintaining their phenotype and a healthy cellular state through an increase in autophagy, particularly when co-cultured with healthy fibroblasts. Conversely, cultured fibroblasts from Zmpste24-/- mice show nuclear defects and acquire a senescent phenotype, characterized by mTORC1 activation and reduced autophagy, which in turn impairs organoid formation. Moreover, these progenitor cells become increasingly susceptible to mechanical stress with aging due to reduced nuclear lamins and the Zmpste24 defect. This vulnerability is illustrated by FACS sorting, which can further compromise their regenerative potential. Our results indicate that, in aging, progenitor cells and their fibroblast niche integrate microenvironmental signals that shape cell-cell interactions essential for lung regeneration.

cell biology↗

bioRxiv2023

Peripheral Blood Single-Cell Sequencing Uncovers Common and Specific Immune Aberrations in Fibrotic Lung Diseases

Rationale and ObjectivesThe extent and commonality of peripheral blood immune aberrations in fibrotic interstitial lung diseases are not well characterized. In this study, we aimed to identify common and distinct immune aberrations in patients with idiopathic pulmonary fibrosis (IPF) and fibrotic hypersensitivity pneumonitis (FHP) using cutting-edge single-cell profiling technologies. MethodsSingle-cell RNA sequencing was performed on patients and healthy controls peripheral blood and bronchoalveolar lavage samples using 10X Genomics 5 gene expression and V(D)J profiling. Cell type composition, transcriptional profiles, cellular trajectories and signaling, and T and B cell receptor repertoires were studied. The standard Seurat R pipeline was followed for cell type composition and differential gene expression analyses. Transcription factor activity was imputed using the DoRothEA-VIPER algorithm. Pseudotime analyses were conducted using Monocle3, while RNA velocity analyses were performed with Velocyto, scVelo, and CellRank. Cell-cell connectomics were assessed using the Connectome R package. V(D)J analyses were conducted using CellRanger and Immcantation frameworks. Across all analyses, disease group differences were assessed using the Wilcoxon rank-sum test. Measurements and Main Results327,990 cells from 83 samples were profiled. Overall, changes in monocytes were common to IPF and FHP, whereas lymphocytes exhibited disease-specific aberrations. Both diseases displayed enrichment of CCL3hi/CCL4hi CD14+ monocytes (p<2.2e-16) and S100Ahi CD14+ monocytes (p<2.2e-16) versus controls. Trajectory and RNA velocity analysis suggested that pro-fibrotic macrophages observed in BAL originated from peripheral blood monocytes. Lymphocytes exhibited disease-specific aberrations, with CD8+ GZMKhi T cells and activated B cells primarily enriched in FHP patients. V(D)J analyses revealed unique T and B cell receptor complementarity-determining region 3 (CDR3) amino acid compositions (p<0.05) in FHP and significant IgA enrichment in IPF (p<5.2e-7). ConclusionsWe identified common and disease-specific immune mechanisms in IPF and FHP; S100Ahi monocytes and SPP1hi macrophages are common to IPF and FHP, whereas GMZKhi T lymphocytes and T and B cell receptor repertoires were unique in FHP. Our findings open novel strategies for the diagnosis and treatment of IPF and FHP.

genomics↗

bioRxiv2019

PulmonDB: a curated lung disease gene expression database

Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) have contrasting clinical and pathological characteristics, and interesting whole-genome transcriptomic profiles. However, data from public repositories are difficult to reprocess and reanalyze. Here we present PulmonDB, a web-based database (http://pulmondb.liigh.unam.mx/) and R library that facilitates exploration of gene expression profiles for these diseases by integrating transcriptomic data and curated annotation from different sources. We demonstrated the value of this resource by presenting the expression of already well-known genes of COPD and IPF across multiple experiments and the results of two differential expression analyses in which we successfully identified differences and similarities. With this first version of PulmonDB, we create a new hypothesis and compare the two diseases from a transcriptomics perspective.

bioinformatics↗