Biology subjects

Moussy, A.

Publications and source records attributed to Moussy, A..

15 recordsLinked to original sources

bioRxiv2026

Dim blue light drives reversible fucoxanthin derivative accumulation in the pelagophyte Pelagomonas calceolata

Pigment composition and regulation are critical for efficient photosynthesis in the ocean, where light intensity decreases and the spectrum narrows with depth. Fucoxanthin (Fx), the main carotenoid of several microalgal lineages, harvests the blue-green light prevailing in the deep euphotic zone. In pelagophytes, the acylated derivative 19'-butanoyloxyfucoxanthin (19'-BFx) is abundant, yet its function and regulation remain unclear. Here, we investigated how irradiance and spectral quality shape photoacclimation in Pelagomonas calceolata, an abundant and cosmopolitan low-light pelagophyte. Cultures were grown under blue or white light across 2-60 umol photons m^-2 s^-1. We analysed growth, PSII photophysiology, pigment composition, gene expression levels, and the impact of spectral shifts on the 19'-BFx/Fx ratio. Pelagomonas calceolata grew optimally under dim blue light and displayed low non-photochemical quenching (NPQ) under assay conditions. Transcriptomes revealed broad remodelling driven mainly by irradiance and modulated by light colour, including carotenoid-related processes. Dim blue light progressively increased the 19'-BFx/Fx ratio, whereas white light kept it low and reversed the response after a blue-to-white shift. These results identify reversible, spectrum-dependent 19'-BFx accumulation as a key component of photoacclimation in P. calceolata and separate irradiance-driven from spectrum-dependent cellular responses. This plasticity may explain the ecological success of P. calceolata in low-light oceans.

plant biology↗

bioRxiv2026

Kruppel-like factors KLF5 & KLF8 emerge as master transcriptional regulators of Alzheimers disease, as revealed on cell fate regulomes in human brain organoids

In addition to the well described beta-amyloid plates accumulation and tau hyper-phosphorylation, Alzheimers disease (AD) is accompanied by major changes in gene expression. Herein, we aimed at revealing master transcription factors (TFs) responsible for gene expression changes during AD progression. For this, we have used human brain organoids (BORGs) harbouring AD-related genetic mutations (APP-Swedish, PSEN1-M146V), which were traced over multiple time-points by bulk and spatially-resolved transcriptomics. By reconstructing gene regulatory networks (GRNs) that recapitulate BORG development, we have identified a subset of 110 AD-specific master TFs, and for 75 of them we retrieved KLF5 and/or KLF8 binding motifs within their promoters. Furthermore, 64 of the AD-specific TFs found in BORGs are significantly over-expressed on AD human patients samples, confirming the relevance of these factors beyond the context of the familial genetic mutations. Finally, we have demonstrated that this AD-specific regulome is at least partially controlled by the aberrant CREB3L2-ATF4 heterodimer previously described as being induced by the beta-amyloid plates deposition. Overall, these findings reconstitute the regulome behind the progression of AD and highlights key TFs as potential druggable targets for the treatment of the disease.

systems biology↗

bioRxiv2026

Masitinib is an oral, brain penetrant inhibitor of microglial and mast cell activity with neuroprotective potential in progressive forms of multiple sclerosis

IntroductionProgressive multiple sclerosis (MS), including primary progressive MS (PPMS) and non-active secondary progressive MS (nSPMS), remains an unmet need, as few treatments target innate immune pathways. Masitinib (AB1010) is a selective tyrosine kinase inhibitor that targets c-Kit and colony-stimulating factor 1 receptor pathways. This mechanism disrupts mast cell-microglia interactions, key innate immune effectors in progressive MS pathogenesis, reducing neuroinflammation and neuronal damage. In the phase 3 AB07002 trial, masitinib (4.5 mg/kg/d) over 96 weeks met its primary endpoint. Comparable signals in PPMS and nSPMS indicated masitinib benefited both phenotypes. Secondary analyses showed that masitinib lowered the progression to wheelchair dependence (EDSS [≥]7.0, 12 weeks) and reduced the 12-week confirmed EDSS progression risk by 37% versus placebo. MethodsThis study aimed to confirm that oral masitinib achieves central nervous system (CNS) concentrations sufficient to modulate CSF1R and wild-type c-Kit, thereby underpinning its neuroprotective potential. Male Sprague Dawley rats (n=12, [~]200 g) were administered a single oral dose (30 mg/kg). Plasma and brain samples were collected at 2, 4, 8, and 24 hours post-dose (n=3 per time point). Masitinib (AB1010) and its metabolite (AB3280) were quantified in plasma and brain homogenates using LC-MS/MS. ResultsMasitinib reached a brain Cmax of 223.5 ng/mL ([~]450 nM), exceeding IC50 values for CSF1R and wild-type c-KIT by [~]5-fold and 2-fold, respectively, indicating effective CNS target engagement. The active metabolite AB3280 also achieved brain Cmax levels with full inhibitory activity. Masitinib demonstrated consistent CNS penetration supported by a proportional plasma-to-brain exposure relationship. ConclusionMasitinibs favorable CNS penetration and safety profile, alongside its unique mast cell inhibition, position it as a compelling candidate for progressive MS treatment, either as monotherapy or in combination with other agents. This multifaceted immunomodulatory approach addresses critical unmet needs in progressive MS and supports further clinical development.

neuroscience↗

bioRxiv2026

HIDDEN APICOMPLEXAN PARASITE DIVERSITY LINKS CORAL AND PLANKTON MICROBIOMES ACROSS REEF SEASCAPES

Parasitism is one of the most widespread trophic strategies in nature, though its diversity and ecological distribution in marine ecosystems remain poorly characterized. Apicomplexa are a major clade of obligate parasites best known for medically important taxa, yet their diversity and distribution in the ocean is still largely unresolved. Here, we used metabarcoding data from the Tara expeditions to investigate the diversity, distribution, and environmental drivers of Apicomplexa across coral reef ecosystems and adjacent oceanic habitats. By integrating samples spanning planktonic communities, coral tissues, and marine sediments across multiple oceanic regions, we substantially expand the known phylogenetic breadth of marine apicomplexans. Although apicomplexans were generally low in relative abundance, they were widely distributed across marine environments. Community composition differed markedly among habitats. Corallicolid lineages were consistently associated with coral hosts, whereas planktonic samples harbored a greater diversity of apicomplexans, dominated by crustacean-associated gregarines. Sediments contained particularly high apicomplexan richness, including several poorly characterized groups. Capitalizing on the pan-Pacific transect of the expedition, we resolved biogeographic patterns in apicomplexan diversity across ocean basins: tropical regions showed the highest overall diversity, while polar environments contained distinct apicomplexan assemblages not detected in other ocean biomes. Together, these results highlight the extensive and previously underappreciated diversity of marine Apicomplexa and demonstrate that integrating multiple marine biomes is essential for resolving the phylogenetic and ecological breadth of parasitism in the ocean.

genomics↗

bioRxiv2026

Ocean-scale transcriptomic analysis of corallicolids (Apicomplexa) reveals their ubiquity and molecular interactions with Pocillopora corals.

Corals are complex holobionts, encompassing numerous prokaryotes, viruses, and protists. This associated microbial community strongly influences coral health and its resilience to global ocean warming. Corallicolid apicomplexans are widespread coral-infecting parasites, yet their impact on the coral host remains poorly understood. This knowledge gap largely stems from the low abundance of these parasites in coral tissues, which makes them difficult to isolate and access to their genetic material. Here we analyzed nearly 1,000 Pocillopora coral colonies collected from 32 islands during the Tara Pacific expedition to identify the drivers of corallicolid prevalence and abundance. Corallicolids were detected in almost all Pocillopora colonies with variable relative abundances between islands. The high abundance of specific corallicolid populations correlates with seawater temperature and levels of host protein carbonylation. We used a large collection of 297 metatranscriptomes to assemble a corallicolid transcriptome and we identified apicomplexan parasite signature genes, including the GRA9 and PV2 confirming the close phylogenetic relationship with the family of Eimeriidae. Gene expression patterns indicate that the high abundance of corallicolids correlates with a high transcription of genes encoding apical complex proteins and genes involved in the control of host immune defenses. Overall, this study provides new insights into corallicolid biology and its interaction with the coral host by combining a newly generated transcriptome with a large-scale sampling of Pocillopora corals across the Pacific Ocean.

genomics↗

bioRxiv2025

Identification of AB8939, a novel synthetic microtubule destabilizer and ALDH inhibitor that overcomes multidrug resistance in tumor cells as a drug candidate for the treatment of refractory acute myeloid leukemia

We identified AB8939, a novel small synthetic molecule that exhibits strong and broad antiproliferative activity against a panel of various cancer cell types with IC50 values in the nanomolar range. In vitro investigations showed that AB8939 is a novel microtubule-targeting agent that interacts with the colchicine-binding site of tubulin. AB8939 disrupts the microtubule network, leading to mitotic arrest in G2/M phase and subsequent apoptosis. Importantly, AB8939 overcomes drug resistance mechanisms, including overexpression of efflux transporters such as P-glycoprotein (P-gp) and aberrant expression of {beta}3-tubulin. AB8939 displays high cytotoxicity against blasts from AML patients, including blasts resistant to cytarabine (Ara-C). In vivo, AB8939 shows strong antitumor activity in MOLM-14, an Ara-C-resistant AML model, as evidenced by tumor growth inhibition and substantial increase in mouse survival. Further experiments performed on an AML PDX TG-AML-36 model demonstrated that AB8939 efficiently kills leukemic stem cells (CD34+/CD38-). Reverse proteomic experiments revealed that AB8939 inhibits ALDH1 and ALDH2, enzymes often overexpressed in tumors and tumor stem cells, thereby favoring tumor progression and relapse. AB8939 is a novel dual-targeting drug that acts on both tubulin and ALDH enzymes, with potential activity against various cancer types, especially refractory AML with complex karyotypes such as those displaying MECOM rearrangement and AML with mutations associated with poor prognosis, such as ASXL1 and TP53.

cell biology↗

bioRxiv2025

The JEDI marker as a universal measure of planetary biodiversity

Despite its critical importance in the formation and maintenance of ecosystems and homeostasis on Earth, biodiversity remains a complex and non-unified concept. Consequently, standards for measuring global biodiversity are lacking, hindering our capacity to document Earths biota and track its change. Here, we propose the Joint, cellular life-Encompassing DIversity (JEDI) marker as a simple, effective and quantitative measure to assess and monitor biodiversity. The JEDI marker is a ribosomal RNA gene fragment that can be amplified from all domains of life using a single pair of PCR primers. We demonstrate the applicability and effectiveness of this approach for assessing biodiversity across ecological and biological scales, from holobionts to diverse ecosystems. In addition, we provide an automated bioinformatic workflow to support the standardised and reproducible analysis of the JEDI marker in future studies. While this approach is not free from trade-offs, we argue that its advantages outweigh its limitations by providing a unique, operational and scalable solution that builds on established infrastructure to integrate the microbial majority into biodiversity assessments and provide fundamental insights into organismal dynamics and associations across domains of life. Thus, the JEDI marker approach addresses the urgent need for a universal and standardised framework to effectively measure and monitor biodiversity at planetary scales in an era of profound global change.

ecology↗

bioRxiv2025

ERGA-BGE genome of Noah's Ark shell (Arca noae Linnaeus, 1758), a Mediterranean bivalve species

Arca noae, also known as the Noahs Ark clam, is a bivalve mollusk found in the shallow coastal waters of the Mediterranean Sea and the eastern Atlantic Ocean. This species plays a crucial ecological role by filtering plankton and organic particles from the water, helping maintain water quality and supporting nutrient cycling in marine ecosystems. It is also an important food source for various marine predators, including fish and crustaceans, thereby contributing to the coastal food web. Arca noae is notably resilient to environmental stressors, such as temperature fluctuations, changes in salinity, and pollution, making it a valuable model species for studying how bivalves adapt and respond to stress. While it is not commonly harvested commercially, Arca noae is of great interest to marine researchers due to its ability to thrive in diverse coastal habitats. The reference genome of Arca noae will thus provide important evolutionary insights. The entirety of the genome sequence was assembled into 19 contiguous chromosomal pseudomolecules. This chromosome-level assembly encompasses 1.5 Gb, composed of 257 contigs and 119 scaffolds, with contig and scaffold N50 values of 20.5 Mb and 84.7 Mb, respectively.

genomics↗

bioRxiv2025

ERGA-BGE genome of Androsace saussurei Dentant, Lavergne, F. C. Boucher & S. Ibanez, a recently described plant from the rooftops of Europe

The reference genome of Androsace saussurei (Ericales: Primulaceae: Primuloideae) provides a valuable resource for understanding the mechanisms of plant adaptations to the most extreme environments where flowering plants can thrive and the speciation mechanisms of plants dwelling on high alpine sky islands. The entirety of the genome sequence was assembled into 20 contiguous chromosomal pseudomolecules. This chromosome-level assembly encompasses 413 Mb, composed of 253 contigs and 101 scaffolds, with contig and scaffold N50 values of 4.95 Mb and 21.2 Mb, respectively.

genomics↗

bioRxiv2025

ERGA-BGE genome of Pinctada radiata (Leach, 1814): one of the first Lessepsian migrants

Pinctada radiata, commonly known as the Gulf pearl oyster, is a species of pearl oyster found primarily in the warm waters of the Red Sea, the Persian Gulf, and parts of the Indian Ocean. Pinctada radiata contributes to marine ecosystems by filtering water, which helps maintain water quality and supports other marine life. This species is the first bivalve Lessepsian migrant, having migrated from the Red Sea to the Mediterranean Sea via the Suez Canal. The reference genome of Pinctada radiata could help identify genes enabling adaptation to varying temperatures and salinities, facilitating survival in diverse and newly colonized habitats allowing comparisons with other bivalves to uncover shared and unique genetic adaptations. Additionally, the genome could support targeted management practices and conservation initiatives, such as habitat restoration and selective breeding, ensuring the long-term sustainability of P. radiata. The entirety of the genome sequence was assembled into 14 contiguous chromosomal pseudomolecules. This chromosome-level assembly encompasses 0.93 Gb, composed of 220 contigs and 44 scaffolds, with contig and scaffold N50 values of 8.1 Mb and 63.8 Mb, respectively.

genomics↗

bioRxiv2024

Masitinib Limits Neuronal Damage, as Measured by Serum Neurofilament Light Chain Concentration, in a Model of Neuroimmune-Driven Neurodegenerative Disease

BackgroundMasitinib is an orally administered tyrosine kinase inhibitor that targets activated cells of the innate neuroimmune system. We have studied the neuroprotective action of masitinib on the manifestations of experimental autoimmune encephalitis (EAE) induced axonal and neuronal damage. EAE is a model of neuroimmune-driven chronic neuroinflammation and therefore highly relevant to masitinibs mechanism of action in neurodegenerative diseases. Importantly, neuronal damage, or prevention thereof, can be rapidly assessed by measuring serum neurofilament light chain (NfL) concentration in EAE-induced mice. MethodsEAE induction was performed in healthy female C57BL/6 mice via active MOG35-55 peptide immunization. Treatments were initiated 14 days post EAE induction. On day-0, 39 mice with established EAE symptoms were randomly assigned to 3 treatment groups (n=13): EAE control, masitinib 50 mg/kg/day (M50), and masitinib 100 mg/kg/day (M100). Treatment started on day-1 and ended on day-15. Blood samples were collected at day-1, day-8 (via tail vein sampling) and day-15 (via intracardiac puncture). Assessments included quantification of serum NfL levels along the disease duration, cytokine quantification at day-15, and clinical assessments. ResultsMasitinib treatment significantly (p<0.0001) limited NfL production with respect to control; specifically, relative change in serum NfL concentration at day-8 was 43% and 60% lower for the M50 and M100 groups, respectively. Likewise, for the assessment of absolute serum NfL at day-8 and day-15, there was a significantly lower NfL concentration for masitinib treatment as compared with control. Furthermore, EAE mice treated with masitinib showed significantly lower concentrations of several well-established pro-inflammatory cytokines relative to control at day-15. A beneficial effect of masitinib on functional performance was also observed, with both M50 and M100 groups showing significantly less relative deterioration in grip strength at day-15 as compared with control (p<0.001). ConclusionThis study is the first demonstration that masitinib, a drug that targets the innate as opposed to the adaptive neuroimmune system, can lower serum NfL levels, and by extension therefore, neuronal damage, in a neuroimmune-driven neurodegenerative disease model. Overall, findings indicate that masitinib has a neuroprotective effect under conditions of chronic neuroinflammation and therefore plausible disease-modifying activity across a broad range of neurodegenerative diseases.

neuroscience↗

bioRxiv2022

Differentiation is accompanied by a progressive loss in transcriptional memory

Cell differentiation requires the integration of two opposite processes, a stabilizing cellular memory, especially at the transcriptional scale, and a burst of gene expression variability which follows the differentiation induction. Therefore, the actual capacity of a cell to undergo phenotypic change during a differentiation process relies upon a modification in this balance which favors change-inducing gene expression variability. However, there are no experimental data providing insight on how fast the transcriptomes of identical cells would diverge on the scale of the very first two cell divisions during the differentiation process. In order to quantitatively address this question, we developed different experimental methods to recover the transcriptomes of related cells, after one and two divisions, while preserving the information about their lineage at the scale of a single cell division. We analyzed the transcriptomes of related cells from two differentiation biological systems (human CD34+ cells and T2EC chicken primary erythrocytic progenitors) using two different single-cell transcriptomics technologies (sc-RT-qPCR and scRNA-seq). We identified that the gene transcription profiles of differentiating sister-cells are more similar to each-other than to those of non related cells of the same type, sharing the same environment and undergoing similar biological processes. More importantly, we observed greater discrepancies between differentiating sister-cells than between self-renewing sister-cells. Furthermore, a continuous increase in this divergence from first generation to second generation was observed when comparing differentiating cousin-cells to self renewing cousin-cells. Our results are in favor of a continuous and gradual erasure of transcriptional memory during the differentiation process.

cell biology↗

bioRxiv2022

Evidence for close molecular proximity between reverting and undifferentiated cells

According to Waddingtons epigenetic landscape concept, the differentiation process can be illustrated by a cell akin to a ball rolling down from the top of a hill (proliferation state) and crossing furrows before stopping in basins or "attractor states" to reach its stable differentiated state. However, it is now clear that some committed cells can retain a certain degree of plasticity and reacquire phenotypical characteristics of a more pluripotent cell state. In line with this dynamic model, we have previously shown that differentiating cells (chicken erythrocytic progenitors (T2EC)) retain for 24 hours the ability to self-renew when transferred back in self-renewal conditions. Despite those intriguing and promising results, the underlying molecular state of those "reverting" cells remains unexplored. The aim of the present study was therefore to molecularly characterize the T2EC reversion process by combining advanced statistical tools to make the most of single cell transcriptomic data. For this purpose, T2EC, initially maintained in a self-renewal medium (0H), were induced to differentiate for 24h (24H differentiating cells); then a part of these cells was transferred back to the self-renewal medium (48H reverting cells) and the other part was maintained in the differentiation medium for another 24h (48H differentiating cells). For each time point, cell transcriptomes were generated using scRT-qPCR and scRNAseq. Our results showed a strong overlap between 0H and 48H reverting cells when applying dimensional reduction. Moreover, the statistical comparison of cell distributions and differential expression analysis indicated no significant differences between these two cell groups. Interestingly, gene pattern distributions highlighted that, while 48H reverting cells have gene expression pattern more similar to 0H cells, they retained traces of their engagement in the differentiation process. Finally, Sparse PLS analysis showed that only the expression of 3 genes discriminates 48H reverting and 0H cells. Altogether, we show that reverting cells return to an earlier molecular state almost identical to undifferentiated cells and demonstrate a previously undocumented physiological and molecular plasticity during the differentiation process, which most likely results from the dynamic behavior of the underlying molecular network.

cell biology↗

bioRxiv2020

Selective silencing rather than targeted activation of gene expression underlies fate choice in human hematopoietic stem cells.

When human cord blood derived CD34+ cells are induced to differentiate in vitro, they undergo rapid and dynamic morphological and molecular transformations that are critical for fate commitment. Using ATAC-seq and single-cell RNA sequencing, we detected two phases in this process. In the first phase, we observed a rapid and global chromatin opening that makes most of the gene promoters in the genome accessible, followed by widespread upregulation of gene transcription and a concomitant increase in the cell-to-cell variability of gene expression. The second phase is marked by a slow chromatin closure and a subsequent overall downregulation of gene transcription and emergence of coherent expression profiles corresponding to distinct cell subpopulations. These observations are consistent with a model based on the spontaneous probabilistic organization of the cellular process of fate commitment.

cell biology↗

bioRxiv2017

Integrated time-lapse and single-cell transcription studies highlight the variable and dynamic nature of human hematopoietic cell fate commitment.

Individual cells take lineage commitment decisions in a way that is not necessarily uniform. We address this issue by characterizing transcriptional changes in cord blood derived CD34+ cells at the single-cell level and integrating data with cell division history and morphological changes determined by time-lapse microscopy. We show, that major transcriptional changes leading to a multilineage-primed gene expression state occur very rapidly during the first cell cycle. One of the two stable lineage-primed patterns emerges gradually in each cell with variable timing. Some cells reach a stable morphology and molecular phenotype by the end of the first cell cycle and transmit it clonally. Others fluctuate between the two phenotypes over several cell cycles. Our analysis highlights the dynamic nature and variable timing of cell fate commitment in hematopoietic cells, links the gene expression pattern to cell morphology and identifies a new category of cells with fluctuating phenotypic characteristics, demonstrating the complexity of the fate decision process, away from a simple binary switch between two options as it is usually envisioned.

cell biology↗