Biology subjects

Mas, A.

Publications and source records attributed to Mas, A..

15 recordsLinked to original sources

bioRxiv2026

An integrated multimodal pan-organ atlas of the female reproductive system across the lifespan contextualises gynaecological pathologies

Single cell transcriptomics has transformed our knowledge of reproductive tissues, yet studies remain largely organ-specific and temporally limited, leaving an incomplete picture of how cell types are distributed across the reproductive system over a lifetime. Gynaecological conditions affect more than one in four females and frequently span multiple organs and life stages. To advance our understanding and treatment of these conditions, an integrated cellular reference is essential. Here we present the Human Female Reproductive System Cell Atlas v1: a single-cell transcriptomic resource integrating more than 2M cells across the ovary, fallopian tube, uterus, cervix and vagina over the lifespan and menstrual cycle, further integrated with spatial transcriptomics and chromatin accessibility profiling to define 210 cell types through community-based annotation. Cross-organ integration resolves shared and organ-specific cellular states, identifying uterine-specific perivascular populations lining uterine spiral arteries, hypoxia-sensing type 3 innate lymphoid cells (ILC3s) enriched in the uterus, and lipid-associated macrophages with distinct subsets in each reproductive organ, including a previously undescribed population shared between the uterus and fallopian tube. Cross-organ integration enables detection of ectopic epithelial populations in otherwise healthy donors, including endometrial-like cells within a paediatric ovary consistent with early endometriosis. Integration with genome-wide association studies (GWAS) reveals that risk variants for major gynecological conditions act in mesenchymal cell states defined by specific transcriptional programmes and spatial or temporal context - for instance, heavy menstrual bleeding risk is enriched in basal fibroblasts (SFRP5) of the regenerative endometrial compartment. An integrated chromatin accessibility atlas provides peak-to-gene maps across reproductive cell types, enabling nomination of disease effector genes and providing the first regulatory evidence linking a Polyendocrine Metabolic Ovarian Syndrome (PMOS) risk locus to INHBB in granulosa cells. Together, this resource establishes a cellular and molecular framework for reproductive biology and the pathogenesis of neglected gynaecological conditions.

Cell Biology↗

bioRxiv2026

Full-thickness spatial transcriptomics of the human uterus reveals basalis niche architecture and regeneration gradients during menstrual breakdown

The human endometrium (uterine lining) undergoes cyclical breakdown and scarless regeneration during each menstrual cycle, representing an exceptional model of adult tissue renewal. Regeneration is driven primarily by progenitor cells retained within the deep, basalis compartment during menstruation, yet the full-depth spatiotemporal dynamics of this process have remained understudied due to anatomical and technical limitations. Here, we map spatial gene-expression gradients across the full thickness of the human endometrium, from the myometrial-endometrial boundary to the luminal surface, using high-resolution spatial transcriptomics integrated with single-cell transcriptomics. We profile more than ten million cells from biopsies, hysterectomy samples and menstrual fluid, enriching for the menstrual and proliferative phases, which are underrepresented in previous studies. We show that endometrial breakdown, regeneration and rapid luminal re-epithelialisation are concurrent rather than temporally separated, organised across distinct tissue compartments, revealing a mode of tissue renewal in which shedding and repair operate simultaneously. Continuous basalis-to-luminal transcriptional gradients link progenitor identity, niche signalling, and tissue remodelling, defining a coordinated regenerative axis spanning the full tissue depth. We resolve the basalis epithelial niche at unprecedented molecular resolution, identifying for the first time a discrete, predominantly quiescent progenitor-like epithelial subset and specialised supporting SFRP5+ fibroblasts, both characterised by WNT inhibition, alongside lymphoid aggregates, forming a multi-component architecture that persists after menopause, consistent with a long-lived regenerative reservoir. Together, these findings establish spatial transcriptional gradients as a central organising principle of endometrial renewal, providing a molecular framework for understanding disorders of menstruation, implantation failure, and impaired tissue repair.

cell biology↗

bioRxiv2026

Phosphaphenalene Gold(I) Complexes as Broad-Spectrum Antivirals Against Emerging Flaviruses

Flaviviruses are emerging and re-emerging pathogens of major global health concern that can replicate in hosts of different phyla, including humans. Among them, Zika virus (ZIKV) is associated with severe neurological outcomes, including neonatal microcephaly, congenital malformations, and Guillain-Barre syndrome in adults. Usutu virus (USUV), another mosquito-borne flavivirus, primarily infects birds and has been linked to neurological symptoms in humans. Bagaza virus (BAGV) significantly affects the wildlife of some bird species and carries a noteworthy risk of zoonotic transmission. Despite their clinical significance, approved antiviral options for flaviviral infections (including ZIKV, USUV, and BAGV) are not available, and current management focuses primarily on providing symptomatic relief and supportive care. To address this therapeutic gap, we evaluated the antiviral activity of five phosphaphenalene-based gold (I) complexes. These phosphaphenalene-derived compounds exhibit straightforward and versatile chemistry, allowing access to derivatives with improved stability, bioactivity, selectivity, and cytotoxicity, thereby enhancing their biological activities. Two compounds showed potent inhibition of ZIKV, USUV, and BAGV replication at low micromolar concentrations, with ZIKV displaying greater sensitivity. ZIKV titers were reduced by up to three orders of magnitude in a dose-dependent fashion. Mechanistic studies revealed that both compounds inhibited thioredoxin reductase and disrupted autophagy. This study represents the first demonstration of the potential of phosphaphenalene-based gold (I) complexes as promising candidates against flavivirus infections, offering a promising foundation for the development of urgently needed antiviral therapies with potential impact on global health.

microbiology↗

bioRxiv2026

Isolation and characterization of Bagaza virus: insights into host adaptability and zoonotic potential.

Bagaza virus (BAGV) is an emerging orthoflavivirus that primarily infects wild birds, but its ability to infect other hosts remains poorly understood. We isolated BAGV RNA from the brain of a dead red-legged partridge and evaluated viral adaptation and replication kinetics in avian, mosquito, mammalian, and human cell lines. BAGV replicated efficiently in monkey, mosquito, duck, and selected human cell lines (HEK-293T and Huh7.5), whereas replication was limited in other human, hamster, and chicken fibroblast cell lines, indicating variable cellular susceptibility. These differences may reflect host-specific adaptation or distinct innate immune responses. Viral RNA replication complexes localized to the cytoplasm, as shown by immunocytochemical detection of dsRNA. Ribavirin treatment significantly reduced viral titers and RNA levels, demonstrating antiviral sensitivity. Together, these findings provide new insights into BAGV biology, host adaptability, and potential zoonotic risk, and support the development of antiviral strategies and improved epidemiological surveillance within a One Health framework.

microbiology↗

bioRxiv2025

Tunable simultaneous propulsion by two distinct motility motors drives surface motility in bacteria

Motility allows cells to explore their surroundings, evade threats, and coordinate collective behaviors. Many organisms, from bacteria to animals, encode more than one motility system, yet whether and how mechanistically distinct systems are integrated within individual cells remains largely unresolved. We address this question in the predatory bacterium Myxococcus xanthus, which navigates surfaces using two mechanistically and evolutionarily distinct motors: focal-adhesion-based gliding and type IV pili-driven twitching. For this, we develop an imaging-based quantitative behavioral phenotyping method to show that both motors are simultaneously active within individual cells and jointly power cell movement. Cells engaging both motors move faster and explore space more effectively than cells using either motor alone, expanding locomotion performance. Extracellular calcium tunes their relative contributions, progressively shifting cells from gliding- to twitching-dominated propulsion. Unexpectedly, the gliding motor can boost twitching even without anchoring to the surface, revealing that cooperation between motility systems extends beyond simultaneous force generation. Together, these findings reveal that evolutionarily distinct motility systems can function as components of a single, environmentally tunable propulsion strategy.

microbiology↗

bioRxiv2025

In vitro and in vivo Antiviral Activity of the Acyclic Nucleoside Phosphonate Prodrug LAVR-289 against Poxvirus and African Swine Fever Virus Replication

Poxviruses are double-stranded DNA viruses including relevant zoonotic pathogens with high morbidity. Although African swine fever virus (ASFV) belongs to the Asfarviridae family and is not strictly classified as a member of the Poxviridae, both fall within the same class of Pokkesviricetes that replicate in the cytoplasm, and some poxviruses pose potential biological warfare threats. Among compounds targeting these viruses, acyclic nucleoside phosphonate prodrugs are nucleoside analogues inhibitors of viral DNA polymerases that have been identified as promising agents. However, some limitations related to their toxicity and the rapid emergence of resistance highlight the need for new antiviral molecules. In this study, the new nucleoside analogue LAVR-289 was shown to effectively inhibit the viral replication by intervening early in the viral replication step, targeting a specific domain of the poxvirus DNA polymerase. Using monkeypox virus models, the subcutaneous or oral administration of LAVR-289 demonstrates protective efficacy in infected animal models without toxicity or behavioral modification. The stability in vivo, long shelf-life and efficacy make LAVR-289 a promising candidate for further development and stockpiling as a medical countermeasure against dsDNA virus outbreaks. Its broad-spectrum efficacy is a real asset in a context of recurrent viral epidemics, risk of bioterrorism and emergence of resistance strains in the population. HighlightsO_LILAVR-289 is a unique acyclic nucleoside phosphonate prodrug targeting viral DNA polymerases. C_LIO_LILAVR-289 displays antiviral activity against dsDNA viruses, ASFV and poxviruses. C_LIO_LIFirst report of in vivo evaluation of LAVR-289 against MPXV by subcutaneous and oral administration. C_LIO_LILAVR-289 reduces clinical signs and increase survival in animal models. C_LI

microbiology↗

bioRxiv2024

Classification and Regression Trees to predict Transcription Factor Combinatorial Interaction in scRNA-seq data.

Understanding the regulatory mechanisms that govern gene expression is crucial for deciphering cellular functions. Transcription factors (TFs) play a key role in regulating gene expression. In particular TF combinatorial interactions (TFCI) are now thought to largely shape genomic transcriptional responses, but predicting TFCI per se is still a difficult task. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool providing a whole new readout of gene regulatory effects. In this study, we propose a machine learning approach utilizing Classification and Regression Trees (CART) for predicting TFCI in >110k scRNA-seq data points yielded from Arabidopsis thaliana root. The proposed methodology provides a valuable tool for pointing to new TFCI mechanisms and could advance our understanding of Gene Regulatory Networks functioning.

bioinformatics↗

bioRxiv2023

Effect of Aging on the Human Myometrium at Single-Cell Resolution

The myometrial dysfunction associated with aging can prompt complications during pregnancy and labor, causing a 7.8-fold increase in maternal mortality in women over 40. Using single-cell/single-nucleus RNA sequencing and spatial transcriptomics, we constructed a cellular atlas of the aging myometrium from 186,120 cells across twenty peri- and post-menopausal women. We identified 23 myometrial cell subpopulations, including novel contractile capillary, venous capillary, immune-modulated fibroblasts, and nervous system regulatory fibroblasts. Myometrial aging leads to fewer contractile capillary cells, a reduced level of ion channel expression in smooth muscle cells, and impaired gene expression in endothelial, smooth muscle, fibroblast, perivascular, and immune cells. We observed altered myometrial cell-to-cell communication as an aging hallmark associated with the loss of 25/229 signaling pathways, including those related to angiogenesis, tissue repair, contractility, immunity, and nervous system regulation. These insights may contribute to a better understanding of the complications faced by older women during pregnancy and labor.

cell biology↗

bioRxiv2022

Full epistatic interaction maps retrieve part of missing heritability and improve phenotypic prediction

The first Genome Wide Association Studies (GWAS) shed light on the concept of missing heritability. It constitutes a mystery with transcending consequences from plant to human genetics. This mystery lies in the fact that a large proportion of phenotypes are not explained by unique or simple genomic modifications. One has to invoke genetic interactions among different loci, also known as epistasis, to partly account for it. However, current GWAS statistical models are moderately scalable, very sensitive to False Discovery Rate (FDR) corrections and, even combined with High Performance Computing (HPC), they can take years to evaluate for a full combinatorial epistatic space for a single phenotype. Here we propose a modeling approach, named Next-Gen GWAS (NGG) that evaluates, within hours, >60 billions of single nucleotide polymorphism (SNP) combinatorial first-order interactions, on a reasonable computer power. We first benchmark NGG on state of the art GWAS model results, and applied this to Arabidopsis thaliana providing 2D epistatic maps at gene resolution. We demonstrate on several phenotypes that a large proportion of the missing heritability can i) be retrieved with this modeling approach, ii) indeed lies in epistatic interactions and iii) can be used to improve phenotype prediction.

genetics↗

bioRxiv2022

Highly parallelized laboratory evolution of wine yeasts for enhanced metabolic phenotypes

Adaptive Laboratory Evolution (ALE) of microbes can improve the efficiency of sustainable industrial processes important to the global economy, but chance and genetic background effects often lead to suboptimal outcomes. Here we report an ALE platform to circumvent these flaws through parallelized clonal evolution at an unprecedented scale. Using this platform, we clonally evolved 104 yeast populations in parallel from many strains for eight desired wine production traits. Expansions of both ALE replicates and lineage numbers broadened the evolutionary search spectrum and increased the chances of evolving improved wine yeasts unencumbered by unwanted side effects. ALE gains often coincided with distinct aneuploidies and the emergence of semi-predictable side effects that were characteristic of each selection niche. Many high performing ALE strains retained their desired traits upon transfer to industrial conditions and produced high quality wine. Overall, our ALE platform brings evolutionary engineering into the realm of high throughput science and opens opportunities for rapidly optimizing microbes for use in many industrial sectors which otherwise could take many years to accomplish.

bioengineering↗

bioRxiv2021

Predictive evolution of metabolic phenotypes using model-designed selection niches

Traits lacking fitness benefit cannot be directly selected for under Darwinian evolution. Thus, features such as metabolite secretion are currently inaccessible to adaptive laboratory evolution. Here, we utilize environment-dependency of trait correlations to enable Darwinian selection of fitness-neutral or costly traits. We use metabolic models to design selection niches and to identify surrogate traits that are genetically correlated with cell fitness in the selection niche but coupled to the desired trait in the target niche. Adaptive evolution in the selection niche and subsequent return to the target niche is thereby predicted to enhance the desired trait. We experimentally validate the theory by evolving Saccharomyces cerevisiae for increased secretion of aroma compounds in wine fermentation. Genomic, transcriptomic, and proteomic changes in the evolved strains confirmed the predicted flux re-routing to aroma biosynthesis. The use of model-designed selection niches facilitates the predictive evolution of fitness-costly traits for ecological and biotechnological applications.

systems biology↗

bioRxiv2020

Evolution of molecular determinants for SUMO-activating enzyme subcellular localization in plants

Post-translational modification by Small Ubiquitin-related Modifier (SUMO) is an essential regulatory mechanism in eukaryotes. In the cell, SUMO conjugates are highly enriched in the nucleus and, consistently, SUMOylation machinery components are mainly nuclear. Nonetheless, cytosolic SUMO targets also exist and the mechanisms that facilitate SUMO conjugation in the cytosol are unknown. Here, we show that the nuclear localization of the Arabidopsis SUMO activating enzyme large subunit SAE2 is dependent on two nuclear localization signals, the canonical NLS1 and the non-canonical NLS2 identified and validated here. NLS2 is proteolytic processed from SAE2 during seed development, facilitating SAE2 enrichment in the cytosol. Results obtained using transgenic plants expressing different SAE2 proteoforms suggest that SAE2 cytosolic enrichment could constitute a rapid signal for growth arrest. Phylogenetic studies indicated that the Arabidopsis NLS1-NLS2 structural organization is conserved only in seed plants, providing a potential evolutionary role of cytosolic SUMOylation in seed appearance.

biochemistry↗

bioRxiv2020

Guanosine inhibits hepatitis C virus replication and increases indel frequencies, associated with altered intracellular nucleotide pools

In the course of experiments aimed at deciphering the inhibition mechanism of mycophenolic acid and ribavirin in hepatitis C virus (HCV) infection, we observed an inhibitory effect of the nucleoside guanosine (Gua). Here, we report that Gua and not the other standard nucleosides inhibits HCV replication in human hepatoma cells. Gua did not directly inhibit the in vitro polymerase activity of NS5B, but it modified the intracellular levels of nucleoside di- and tri-phosphate (NDPs and NTPs), leading to deficient HCV RNA replication and reduction of infectious progeny virus production. Changes in the concentrations of NTP or NDP modified NS5B RNA polymerase activity in vitro, in particular de novo RNA synthesis and template switching. Furthermore, the Gua-mediated changes were associated with a significant increase in the number of indels in viral RNA, which may account for the reduction of the specific infectivity of the viral progeny, suggesting the presence of defective genomes. Thus, a proper NTP:NDP balance appears to be critical to ensure HCV polymerase fidelity and minimal production of defective genomes. Author summaryRibonucleoside metabolism is essential for replication of RNA viruses. In this article we describe the antiviral activity of the natural ribonucleoside guanosine (Gua). We demonstrate that hepatitis C virus (HCV) replication is inhibited in the presence of increasing concentrations of this ribonucleoside and that this inhibition does not occur as a consequence of a direct inhibition of HCV polymerase. Cells exposed to increasing concentrations of Gua show imbalances in the intracellular concentrations of nucleoside-diphosphates and triphosphates and as the virus is passaged in these cells, it accumulates mutations that reduce its infectivity and decimate its normal spreading capacity.

microbiology↗

bioRxiv2019

Brettanomyces bruxellensis wine isolates show high geographical dispersal and long remanence in cellars

Brettanomyces bruxellensis is the main wine spoiler yeast all over the world, yet the structuration of the populations associated with winemaking remains elusive. In this work, we considered 1411 wine isolates from 21 countries that were genotyped using twelve microsatellite markers. We confirmed that B. bruxellensis isolates from wine environments show high genetic diversity, with 58 and 42% of triploid and diploid individuals respectively distributed in 5 main genetic groups. The distribution in the genetic groups varied greatly depending on the country and/or the wine-producing region. However, the two wine triploid groups showing sulfite resistance/tolerance were identified in almost all regions/countries. Genetically identical isolates were also identified. The analysis of these clone groups revealed that a given genotype could be isolated repeatedly in the same winery over decades, demonstrating unsuspected remanence ability. Besides cellar residency, a great geographic dispersal was also evidenced, with some genotypes isolated in wines from different continents. Finally, the study of old isolates and/or isolates from old vintages revealed that only the diploid groups were identified prior 1990 vintages. The triploid groups were identified in subsequent vintages, and their proportion has increased steadily these last decades, suggesting adaptation to winemaking practices such as sulfite use. A possible evolutionary scenario explaining these results is discussed.

genetics↗

bioRxiv2019

Senolytic treatment targets aberrant p21-expression to restore liver regeneration in adult mice

Young mammals possess a limited regenerative capacity in tissues such as the liver, heart and limbs, but which is quickly lost upon maturation or transition to adulthood. Chronic cellular senescence is a known mediator of decreased tissue function in aging and disease. Here we investigated whether senescence plays a role in the progressive loss of liver regenerative capacity that develops in young adult mice. We find that following partial hepatectomy, the senescence markers p21, p16Ink4a and p19Arf become dynamically expressed at an age when regenerative capacity decreases. In addition, we demonstrate that treatment with a senescence-inhibiting drug improves regenerative capacity, through targeting of aberrant p21 expression. Surprisingly, we also find that the senescence marker p16Ink4a is expressed in a different cell-population to p21, and is unaffected by senescence targeting. This work suggests that senescence may initially develop as a heterogeneous cellular response, and that treatment with senolytic drugs may aid in promoting organ regeneration.

cell biology↗