Biology subjects

Leroy, S.

Publications and source records attributed to Leroy, S..

8 recordsLinked to original sources

bioRxiv2025

Brain size reduction in dogs was already established at least by the Late Neolithic of western Europe, 5,000 years ago

The timing and causes of brain size reduction in domestic dogs remain uncertain. Using endocasts volume as a proxy for brain size, this study provides a first insight into long-term brain size evolution in the wolf-dog lineage. We compared endocranial volumes of 185 modern and 22 prehistoric wolves and dogs ranging from Western Europe to Australia, and spanning the Pleniglacial (35 Ky BP) to the Late Neolithic (5 Ky BP). Our results reveal that Pleistocene so called "protodogs" show no brain size reduction compared to coeval Pleistocene wolves. Instead, we observed a slightly larger relative endocranial volume in the 35,000-year-old protodog from Goyet, which could suggest increased behavioural flexibility in the presence of humans. This hypothesis needs to be tested further. In contrast, Late Neolithic dogs show a drastic 46% brain size reduction with an endocranial volumes comparable to modern small terrier and toy breeds. The anxious and wary temperaments of these Late Neolithic dogs, induced by the brain tissue reorganization associated with such a size reduction, could have served an alerting purpose, among the many other potential roles dogs could have played within this Late Neolithic socio-ecosystems.

zoology↗

bioRxiv2025

Escobase and AcR: Escherichia coli databases of genomes and acid resistance genes from isolates from cattle farms

Escherichia coli is a gram-negative bacterium commonly found in mammals and birds intestinal microbiota. It can be easily isolated and has been studied for more than nine decades, making it an ideal model organism. It is mainly commensal but occasionally pathogenic, expressing virulence factors, antibiotic-resistance and acid-resistance genes, which contribute to its ability to persist and colonize diverse environments. Its multi-resistance, combined with the virulence of certain pathotypes (e.g. STEC), poses a recurring threat to public health, as treatment for clinical infections is not always straightforward. The remarkable propensity of E. coli for diversification and genomic variability is often referred to as an open pangenome. This projects objective was to create the Escobase database (Escherichia coli database), which is comprised exclusively of Escherichia coli isolates from cattle farms, allowing us to generate a reference set of genomes that can be used for comparative genomics on samples from cattle and cattle farms. Using the annotated E. coli genomes, we further built a catalog of predicted proteins that help E. coli survive in low pH environments, often encountered when the bacteria traverse through the intestine. We believe these two databases will be of great help to the community, and we plan to keep improving them and publish updated versions in the future.

microbiology↗

bioRxiv2023

Lung injury shifts pulmonary capillary endothelial cells towards regeneration-associated Lrg1+ subpopulations with delayed dynamics in aged mice

Aging increases the risk of developing fibrotic diseases by hampering tissue regeneration after injury. Using longitudinal single-cell RNA-seq and spatial transcriptomics, here we compare the transcriptome of bleomycin-induced fibrotic lungs of young and aged mice, at 3 time points corresponding to the peak of fibrosis, regeneration and resolution. We find that lung injury shifts the transcriptomic profiles of three pulmonary capillary endothelial cells (PCEC) subpopulations. The associated signatures are linked to pro-angiogenic signaling with strong Lrg1 expression and do not progress similarly throughout the resolution process between young and old animals. Moreover, part of this set of resolution-associated markers is also detected in PCEC from samples of patients with idiopathic pulmonary fibrosis. Finally, we find that aging also alters the transcriptome of PCEC which display typical pro-fibrotic and pro-inflammatory features. We propose that age-associated alterations in specific PCEC subpopulations may interfere with the process of lung progenitor differentiation, thus contributing to the persistent fibrotic process typical of human pathology.

pathology↗

bioRxiv2023

Spatially localized expression of glutamate decarboxylase gadB in Escherichia coli O157:H7 microcolonies in hydrogel matrix

Functional diversity within isogenic spatially organized bacterial populations has been shown to trigger emergent community properties such as stress tolerance. Taking advantage of confocal laser scanning microscopy combined with a transcriptional fluorescent fusion reporting at single cell scale the expression of the glutamic acid decarboxylase gadB in E. coli O157:H7, it was possible to visualize for the first-time spatial patterns of bacterial gene expression in microcolonies grown in a gelled matrix. The gadB gene is involved in E. coli tolerance to acidic conditions and its strong over-expression was observed locally on the periphery of embedded microcolonies grown in acidic hydrogels. This spatialization of gadB expression did not correlate with live/dead populations that appeared randomly distributed in the colonies. While the planktonic population of the pathogens was eradicated by an exposition to a pH of 2 (HCl) for 4h, mimicking a stomachal acidic stress, bacteria grown in gel-microcolonies were poorly affected by this treatment, in particular in conditions where gadB was spatially overexpressed. Consequences of these results for food safety are further discussed.

microbiology↗

bioRxiv2022

Activation of the P2RX7/IL-18 pathway in immune cells inhibits lung fibrosis

Idiopathic pulmonary fibrosis (IPF) is an aggressive interstitial lung disease associated with progressive and irreversible deterioration of respiratory functions that lacks curative therapies. Despite IPF being associated with a dysregulated immune response, current antifibrotics aim only at limiting fibroproliferation. We show here that the P2RX7/IL-18/IFNG axis is downregulated in IPF patients and that P2RX7 has immunoregulatory functions. Using our positive modulator of P2RX7, we show that activation of the P2RX7/IL-18 axis in immune cells limits lung fibrosis progression in a mouse model by favoring an anti-fibrotic immune environment, with notably an enhanced IL-18-dependent IFN-{gamma} production by lung T cells leading to a decreased production of IL-17 and TGF{beta}. Overall, we show the ability of the immune system to limit lung fibrosis progression by targeting the immunomodulator P2RX7. Hence, treatment with a small activator of P2RX7 may represent a promising strategy to help patients with lung fibrosis.

immunology↗

bioRxiv2019

A single-cell atlas of the human healthy airways

RationaleThe respiratory tract constitutes an elaborated line of defense based on a unique cellular ecosystem. Single-cell profiling methods enable the investigation of cell population distributions and transcriptional changes along the airways. MethodsWe have explored cellular heterogeneity of the human airway epithelium in 10 healthy living volunteers by single-cell RNA profiling. 77,969 cells were collected by bronchoscopy at 35 distinct locations, from the nose to the 12th division of the airway tree. ResultsThe resulting atlas is composed of a high percentage of epithelial cells (89.1%), but also immune (6.2%) and stromal (4.7%) cells with peculiar cellular proportions in different sites of the airways. It reveals differential gene expression between identical cell types (suprabasal, secretory, and multiciliated cells) from the nose (MUC4, PI3, SIX3) and tracheobronchial (SCGB1A1, TFF3) airways. By contrast, cell-type specific gene expression was stable across all tracheobronchial samples. Our atlas improves the description of ionocytes, pulmonary neuro-endocrine (PNEC) and brush cells, which are likely derived from a common population of precursor cells. We also report a population of KRT13 positive cells with a high percentage of dividing cells which are reminiscent of "hillock" cells previously described in mouse. ConclusionsRobust characterization of this unprecedented large single-cell cohort establishes an important resource for future investigations. The precise description of the continuum existing from nasal epithelium to successive divisions of lung airways and the stable gene expression profile of these regions better defines conditions under which relevant tracheobronchial proxies of human respiratory diseases can be developed.

genomics↗

bioRxiv2018

Single-cell RNA sequencing reveals novel cell differentiation dynamics during human airway epithelium regeneration

BackgroundIt is usually considered that the upper airway epithelium is composed of multiciliated, goblet, secretory and basal cells, which collectively constitute an efficient first line of defense against inhalation of noxious substances. Upon injury, regeneration of this epithelium through proliferation and differentiation can restore a proper mucociliary function. However, in chronic airway diseases, the injured epithelium frequently displays defective repair leading to tissue remodeling, characterized by a loss of multiciliated cells and mucus hyper-secretion. Delineating drivers of differentiation dynamics and cell fate in the human airway epithelium is important to preserve homeostasis.\n\nResultsWe have used single cell transcriptomics to characterize the sequence of cellular and molecular processes taking place during human airway epithelium regeneration. We have characterized airway subpopulations with high resolution and lineage inference algorithms have unraveled cell trajectories from basal to luminal cells, providing markers for specific cell populations, such as deuterosomal cells, i.e. precursors of multiciliated cells. We report that goblet cells, like secretory cells, can act as precursors of multiciliated cells. Our study provides a repertoire of molecules involved in key steps of the regeneration process, either keratins or components of the Notch, Wnt or BMP/TGF{beta} signaling pathways. Our findings were confirmed in independent experiments performed on fresh human and pig airway samples, and on mouse tracheal epithelial cells.\n\nConclusionsOur single-cell RNA-seq study provides novel insights about airway epithelium differentiation dynamics, clarifies cell trajectories between secretory, goblet and multiciliated cells, identifies novel cell subpopulations, and maps the activation and repression of key signaling pathways.

cell biology↗

bioRxiv2018

Targeting the DNM3OS / miR-199a~214 cluster for the treatment of fibroproliferative diseases

Given the paucity of effective treatments for fibrotic disorders, new insights into the deleterious mechanisms controlling fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies. Here, we identified the long non-coding RNA DNM3OS as a critical downstream effector of TGF-{beta}-induced myofibroblast activation. Mechanistically, DNM3OS regulates this process in trans by giving rise to 3 distinct profibrotic mature miRNAs (i.e. miR-199a-5p/3p and miR-214-3p), which influence both SMAD and non-SMAD components of TGF-{beta} signaling in a multifaceted way, through two modes of action consisting of either signal amplification or mediation. Finally, we provide preclinical evidence that interfering with DNM3OS function using distinct strategies not only prevents lung and kidney fibrosis but also improves established lung fibrosis, providing thus a novel paradigm for the treatment of refractory fibrotic diseases such as idiopathic pulmonary fibrosis.\n\nOne Sentence SummaryThe DNM3OS lncRNA is a reservoir of fibromiRs with major functions in fibroblast response to TGF-{beta} and represents a valuable therapeutic target for refractory fibrotic diseases such as idiopathic pulmonary fibrosis (IPF).

pathology↗