Biology subjects

Chaib, S.

Publications and source records attributed to Chaib, S..

8 recordsLinked to original sources

bioRxiv2026

Chilling injury to algal symbionts induces host starvation and metabolic reorganization in a temperate cnidarian

Global temperature anomalies increasingly disrupt the cnidarian-algal symbiosis through a phenomenon termed bleaching. In contrast to heat stress, the mechanisms underlying symbiotic breakdown under cold stress remain largely unknown. Combining physiological and metabolomic measurements, we investigated the response of the photosymbiotic sea anemone holobiont Aiptasia couchii to an experiment mimicking a cold spell in the Mediterranean Sea. Within four weeks, we observed the onset of symbiotic breakdown reflected in reduced algal endosymbiont density and chlorophyll a content. While photosynthetic efficiency remained largely unaffected, no gross photosynthesis was detectable in cold-stressed anemones and decreases in glycosyldiacylglycerols and fatty acyl glycosides indicated chloroplast lipid remobilization. This breakdown of symbiotic carbon cycling was reflected in increased dipeptide and ceramide levels suggesting anemones catabolized protein reserves and induced pre-apoptotic pathways. Taken together, these responses suggest a decoupling of light and dark reactions of photosynthesis in cold-stressed endosymbionts, resembling chilling injury in higher plants and free-living microalgae. This chilling-induced collapse of symbiotic nutrient cycling eventually leads to host starvation in cold-stressed Cnidaria. Hence, while cold and heat stress may invoke contrasting physiological effects on endosymbionts, our results suggest that both stressors destabilize the symbiosis through similar mechanisms culminating in host starvation.

ecology↗

bioRxiv2026

A cryptic hybrid zone reveals the genomic basis of flower colour variation in a plant with a large and complex genome

Flower colour is known to be a classic magic trait, undergoing divergent selection pressures exerted by distinct pollinators and involved in reproductive isolation. However, variation at this trait may also results from other eco-evolutionary factors whose interpretation requires throughout context-specific analyses. Here, we investigated the eco-evolutionary causes of pink- and yellow-flowered morphs in Pedicularis comosa where their parapatric ranges form a contact zone in the East of the Pyrenees Mountains. First, we generated a near-chromosome-scale reference genome assembly for this species. We then used a Genotyping By Sequencing approach to infer patterns of genetic diversity and differentiation between populations and morphs at a total of 158 individuals from 11 localities. We found that neutral genetic structure is primarily consistent with geography rather than with colour. However, admixture analyses and clines suggest the existence of a cryptic hybrid zone between morphs. Outlier detection methods and examination of locus-by-locus cline features, then allowed to pinpoint candidate loci to explain colour variation. To gain insight into the functional aspects of these loci, we finally analysed floral transcriptomes and quantified pigments using Liquid Chromatography coupled with Mass Spectrometry (LC-MS) and confirmed the involvement of key genes in the anthocyanin metabolic pathway (e.g. DFR, FLS) and associated pigments (e.g. cyanidin and delphinidin). Our results show that implementing a highly integrative multi-omic approach can allow unraveling the genetic basis and the eco-evolutionary significance of adaptive traits with even very limited previous knowledge, on species with large and complex genomes.

evolutionary biology↗

bioRxiv2025

The Role of Supraoptic Hypothalamic Arginine Vasopressin Neurons in Aging-Associated Water Balance and Thermoregulatory Deficits

Aging disrupts physiological homeostasis, impairing thermoregulation, metabolism, and water balance, but the underlying neural mechanisms remain unclear. Here, we identify arginine vasopressin (AVP) neurons in the supraoptic nucleus (SON) of the hypothalamus as a critical driver of these changes. Using single-nucleus RNA-sequencing of the anterior hypothalamus in young and aged mice, we found Avp to be one of the most upregulated neuronal transcripts with age. Aged SONAVP neurons displayed enlarged size and heightened excitability, features consistent with hyperactivity. Functionally, chemogenetic activation of SONAVP neurons in young mice reproduced aging-associated phenotypes including hypothermia, reduced energy expenditure, and suppressed water intake. Conversely, knockdown of Avp in the SON of aged mice restored water balance, partially improved thermoregulation and systemic metabolism. Pharmacological inhibition of AVP receptors revealed that neuroendocrine release of AVP drives homeostatic deficits, with distinct roles for V1A and V2 receptors. Senolytic drug treatment improved systemic metabolism and reduced inflammaging but does not rescue hypothalamic AVP dysfunction, underscoring a brain autonomous mechanism of age-related physiological failure. Together, our findings establish SONAVP neuronal hyperactivity as a driver of impaired homeostasis with age and suggest that targeted modulation of neuroendocrine AVP signaling may offer a therapeutic strategy to alleviate age-associated water balance defects.

physiology↗

bioRxiv2025

Senolytic-Resistant Senescent Cells Have a Distinct SASP Profile and Functional Impact: The Path to Developing Senosensitizers

The senescent cell (SC) fate is linked to aging, multiple disorders and diseases, and physical dysfunction. Senolytics, agents that selectively eliminate 30-70% of SCs, act by transiently disabling the senescent cell anti-apoptotic pathways (SCAPs), which defend those SCs that are pro-apoptotic and pro-inflammatory from their own senescence-associated secretory phenotype (SASP). Consistent with this, a JAK/STAT inhibitor, Ruxolitinib, which attenuates the pro-inflammatory SASP of senescent human preadipocytes, caused them to become "senolytic-resistant". Administering senolytics to obese mice selectively decreased abundance of the subset of SCs that is pro-inflammatory. In cell cultures, the 30-70% of human senescent preadipocytes or human umbilical vein endothelial cells (HUVECs) that are senolytic-resistant (to Dasatinib or Quercetin, respectively) had increased p16INK4a, p21CIP1, senescence-associated {beta}-galactosidase (SA{beta}gal), {gamma}H2AX, and proliferative arrest similarly to the total SC population (comprising senolytic-sensitive plus -resistant SCs). However, the SASP of senolytic-resistant SCs entailed less pro-inflammatory/ apoptotic factor production, induced less inflammation in non-senescent cells, and was equivalent or richer in growth/ fibrotic factors. Senolytic-resistant SCs released less mitochondrial DNA (mtDNA) and more highly expressed the anti-inflammatory immune evasion signal, glycoprotein non-melanoma-B (GPNMB). Transplanting senolytic-resistant SCs intraperitoneally into younger mice caused less physical dysfunction than transplanting the total SC population. Because Ruxolitinib attenuates SC release of pro-apoptotic SASP factors, while pathogen-associated molecular pattern factors (PAMPs) can amplify the release of these factors rapidly (acting as "senosensitizers"), senolytic-resistant and senolytic-sensitive SCs appear to be interconvertible.

cell biology↗

bioRxiv2024

Profiling microRNA expression during senescence and aging: mining for a diagnostic tool of senescent-cell burden

In the last decade cellular senescence, a hallmark of aging, has come into focus for pharmacologically targeting aging processes. Senolytics are one of these interventive strategies that have advanced into clinical trials, creating an unmet need for minimally invasive biomarkers of senescent cell load to identify patients at need for senotherapy. We created a landscape of miRNA and mRNA expression in five human cell types induced to senescence in-vitro and provide proof-of-principle evidence that miRNA expression can track senescence burden dynamically in-vivo using transgenic p21high senescent cell clearance in HFD fed mice. Finally, we profiled miRNA expression in seven different tissues, total plasma, and plasma derived EVs of young and 25 months old mice. In a systematic analysis, we identified 22 candidate senomiRs with potential to serve as circulating biomarkers of senescence not only in rodents, but also in upcoming human clinical senolytic trials.

molecular biology↗

bioRxiv2022

The efficacy of chemotherapy is limited by intratumoural senescent cells that persist through the upregulation of PD-L2

Anti-cancer therapies often result in a subset of surviving cancer cells that undergo therapy-induced senescence (TIS). Senescent cancer cells strongly modify the intratumoural microenvironment favoring immunosuppression and, thereby, tumour growth. An emerging strategy to optimise current therapies is to combine them with treatments that eliminate senescent cells. To this end, we undertook an unbiased proteomics approach to identify surface markers contributing to senescent cells immune evasion. Through this approach, we discovered that the immune checkpoint inhibitor PD-L2, but not PD-L1, is upregulated across multiple senescent human and murine cells. Importantly, blockade of PD-L2 strongly synergises with genotoxic chemotherapy, causing remission of solid tumours in mice. We show that PD-L2 inhibition prevents the persistence of chemotherapy-induced senescent cells, which exert cell-extrinsic immunomodulatory actions. In particular, upon chemotherapy, tumours deficient in PD-L2 fail to produce cytokines of the CXCL family, do not recruit myeloid-derived suppressor cells (MDSCs) and are eliminated in a CD8 T cell-dependent manner. We conclude that blockade of PD-L2 improves chemotherapy efficacy by reducing the intratumoural burden of senescent cells and their associated recruitment of immunosuppressive cells. These findings provide a novel strategy to exploit vulnerabilities arising in tumour cells as a result of therapy-induced damage and cellular senescence.

cancer biology↗

bioRxiv2022

Iron accumulation drives fibrosis, senescence, and the senescence-associated secretory phenotype

Fibrogenesis is part of a normal protective response to tissue injury that can become irreversible and progressive, leading to fatal diseases. Senescent cells are a main driver of fibrotic diseases through their secretome, known as senescence-associated secretory phenotype (SASP). However, the mechanisms involved in the conversion of damaged cells into senescent cells remain incompletely understood. Here, we report that multiple types of fibrotic diseases in mice and humans are characterized by the accumulation of iron. We show that vascular and hemolytic injuries, through the release of iron, are efficient in triggering senescence and fibrosis. Interestingly, the accumulation of iron is an intrinsic property of senescent cells that does not require an abnormal surge in extracellular iron. Upon damage, cells initiate an iron accumulation response with abundant ferritin-bound iron within lysosomes and high levels of labile iron, the latter being a main driver of senescence-associated ROS and SASP. Finally, we demonstrate that detection of iron by magnetic resonance imaging (MRI) is a powerful non-invasive method to assess fibrotic burden in the kidneys of mice and patients with renal fibrosis. Our findings establish a central role for iron accumulation in senescence and fibrogenesis.

physiology↗

bioRxiv2019

Role for Merlin/NF2 in transcription elongation through interaction with the PAF complex

The PAF complex (PAFC) coordinates transcription elongation and mRNA processing events and its CDC73/parafibromin subunit functions as a tumour suppressor. The NF2/Merlin tumour suppressor functions at the cell cortex and nucleus and is a key mediator of contact inhibition. Here we provide a direct link between nuclear Merlin and transcription elongation controlled by cell-cell adhesion. Merlin interacts with the PAFC in a cell density-dependent manner and tumour-derived inactivating mutations in both Merlin and CDC73 mutually disrupt their interaction. Growth suppression by Merlin requires CDC73 and Merlin regulates PAFC association with chromatin in a subset of genes. We also identify by CDC73 affinity-proteomics a role for FAT cadherins in regulating the Merlin-PAFC interaction. Our results suggest that in addition to its function within the Hippo pathway, nuclear Merlin is part of a tumour suppressor network which coordinates postinitiation steps of the transcription cycle of genes mediating in contact inhibition.

cancer biology↗