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3. Nucleotide diversity of the ZmPox3 maize peroxidase gene: Relationships between a MITE insertion in exon 2 and variation in forage maize digestibility

Author

Rigau Joan, Rogowsky Peter M, Manicacci Domenica, Birolleau-Touchard Christelle, Guillet-Claude Carine, Murigneux Alain, Martinant Jean-Pierre, and Barrière Yves

Subjects
Genetics, QH426-470
Abstract

Abstract Background Polymorphisms were investigated within the ZmPox3 maize peroxidase gene, possibly involved in lignin biosynthesis because of its colocalization with a cluster of QTL related to lignin content and cell wall digestibility. The purpose of this study was to identify, on the basis of 37 maize lines chosen for their varying degrees of cell wall digestibility and representative of temperate regions germplasm, ZmPox3 haplotypes or individual polymorphisms possibly associated with digestibility. Results Numerous haplotypes with high diversity were identified. Frequency of nucleotide changes was high with on average one SNP every 57 bp. Nucleotide diversity was not equally distributed among site categories: the estimated π was on average eight times higher for silent sites than for non-synonymous sites. Numerous sites were in linkage disequilibrium that decayed with increasing physical distance. A zmPox3 mutant allele, carrying an insertion of a transposable element in the second exon, was found in lines derived from the early flint inbred line, F7. This element possesses many structural features of miniature inverted-repeat transposable elements (MITE). The mutant allele encodes a truncated protein lacking important functional sites. An ANOVA performed with a subset of 31 maize lines indicated that the transposable element was significantly associated with cell wall digestibility. This association was confirmed using an additional set of 25 flint lines related to F7. Moreover, RT-PCR experiments revealed a decreased amount of corresponding mRNA in plants with the MITE insertion. Conclusion These results showed that ZmPox3 could possibly be involved in monolignol polymerisation, and that a deficiency in ZmPox3 peroxidase activity seemingly has a negative effect on cell wall digestibility. Also, genetic diversity analyses of ZmPox3 indicated that this peroxidase could be a relevant target for grass digestibility improvement using specific allele introgressions.

Published
2004
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4. Clonal hematopoiesis driven by chromosome 1q/MDM4 trisomy defines a canonical route toward leukemia in Fanconi anemia

Author

Sebert, Marie, Gachet, Stéphanie, Leblanc, Thierry, Rousseau, Alix, Bluteau, Olivier, Kim, Rathana, Ben Abdelali, Raouf, Sicre de Fontbrune, Flore, Maillard, Loïc, Fedronie, Carèle, Murigneux, Valentine, Bellenger, Léa, Naouar, Naira, Quentin, Samuel, Hernandez, Lucie, Vasquez, Nadia, Da Costa, Mélanie, Prata, Pedro H., Larcher, Lise, de Tersant, Marie, Duchmann, Matthieu, Raimbault, Anna, Trimoreau, Franck, Fenneteau, Odile, Cuccuini, Wendy, Gachard, Nathalie, Auger, Nathalie, Tueur, Giulia, Blanluet, Maud, Gazin, Claude, Souyri, Michèle, Langa Vives, Francina, Mendez-Bermudez, Aaron, Lapillonne, Hélène, Lengline, Etienne, Raffoux, Emmanuel, Fenaux, Pierre, Adès, Lionel, Forcade, Edouard, Jubert, Charlotte, Domenech, Carine, Strullu, Marion, Bruno, Bénédicte, Buchbinder, Nimrod, Thomas, Caroline, Petit, Arnaud, Leverger, Guy, Michel, Gérard, Cavazzana, Marina, Gluckman, Eliane, Bertrand, Yves, Boissel, Nicolas, Baruchel, André, Dalle, Jean-Hugues, Clappier, Emmanuelle, Gilson, Eric, Deriano, Ludovic, Chevret, Sylvie, Sigaux, François, Socié, Gérard, Stoppa-Lyonnet, Dominique, de Thé, Hugues, Antoniewski, Christophe, Bluteau, Dominique, Peffault de Latour, Régis, and Soulier, Jean

Published
2023
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6. Short-term exposure to cigarette smoke upregulates cathepsin S and alters expression of tight junction ZO-1.

Author

Estur, Florent, Murigneux, Emilie, David, Alexis, Magnen, Mélia, Saidi, Ahlame, Lalmanach, Gilles, and Lecaille, Fabien

Subjects
*CONNECTIVE tissue cells, *CIGARETTE smoke, *TIGHT junctions, *CELL junctions, *TISSUE remodeling
Abstract

A long-term exposure to cigarette smoke (CS) alters the integrity of airway epithelial barrier, contributes to lung dysfunction, and elicits the expression and activity of lung cathepsin S (CatS), a cysteine protease that participates in the remodeling of connective tissue and cell junctions. Here, we observed that a short-term (4 days) exposure of mice to CS increased the expression and activity of CatS, while the expression level of zonula occludens 1 (ZO-1), an epithelial tight junction protein that stabilizes barrier assembly, was reduced in lung tissue lysates. Present data support that proteolytically active CatS may contribute to the defect of ZO-1 in CS-exposed mice. [ABSTRACT FROM AUTHOR]

Published
2024
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7. Physiological adaptive traits are a potential allele reservoir for maize genetic progress under challenging conditions

Author

Welcker, Claude, Spencer, Nadir Abusamra, Turc, Olivier, Granato, Italo, Chapuis, Romain, Madur, Delphine, Beauchene, Katia, Gouesnard, Brigitte, Draye, Xavier, Palaffre, Carine, Lorgeou, Josiane, Melkior, Stephane, Guillaume, Colin, Presterl, Thomas, Murigneux, Alain, Wisser, Randall J., Millet, Emilie J., van Eeuwijk, Fred, Charcosset, Alain, and Tardieu, François

Published
2022
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9. EBV-associated primary CNS lymphoma occurring after immunosuppression is a distinct immunobiological entity

Author

Gandhi, M.K., Hoang, T., Law, S.C., Brosda, S., O'Rourke, K., Tobin, J.W.D., Vari, F., Murigneux, V., Fink, L., Gunawardana, J., Gould, C., Oey, H., Bednarska, K., Delecluse, S., Trappe, R.U., Merida de Long, L., Sabdia, M.B., Bhagat, G., Hapgood, G., Blyth, E., Clancy, L., Wight, J., Hawkes, E., Rimsza, L.M., Maguire, A., Bojarczuk, K., Chapuy, B., and Keane, C.

Published
2021
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10. The genetic basis of cytoplasmic male sterility and fertility restoration in wheat

Author

Joanna Melonek, Jorge Duarte, Jerome Martin, Laurent Beuf, Alain Murigneux, Pierrick Varenne, Jordi Comadran, Sebastien Specel, Sylvain Levadoux, Kalia Bernath-Levin, François Torney, Jean-Philippe Pichon, Pascual Perez, and Ian Small

Subjects
Science
Abstract

The development of hybrid wheat cultivars is hampered by the lack of an effective way to control male fertility in breeding lines. Here, the authors report the identification of two restorer-of-fertility genes Rf1 and Rf3 that can restore fertility of wheat plants carrying Triticum timopheevii-type cytoplasmic male sterility.

Published
2021
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13. The genome of the endangered Macadamia jansenii displays little diversity but represents an important genetic resource for plant breeding

Author

Priyanka Sharma, Valentine Murigneux, Jasmine Haimovitz, Catherine J. Nock, Wei Tian, Ardashir Kharabian Masouleh, Bruce Topp, Mobashwer Alam, Agnelo Furtado, and Robert J. Henry

Subjects
endangered species, genome assembly, genome diversity, genome sequencing, Proteaceae, wild species, Botany, QK1-989
Abstract

Abstract Macadamia, a recently domesticated expanding nut crop in the tropical and subtropical regions of the world, is one of the most economically important genera in the diverse and widely adapted Proteaceae family. All four species of Macadamia are rare in the wild with the most recently discovered, M. jansenii, being endangered. The M. jansenii genome has been used as a model for testing sequencing methods using a wide range of long read sequencing techniques. Here, we report a chromosome level genome assembly, generated using a combination of Pacific Biosciences sequencing and Hi‐C, comprising 14 pseudo‐molecules, with a N50 of 52 Mb and a total genome assembly size of 758 Mb of which 56% is repetitive. Completeness assessment revealed that the assembly covered −97.1% of the conserved single copy genes. Annotation predicted 31,591 protein coding genes and allowed the characterization of genes encoding biosynthesis of cyanogenic glycosides, fatty acid metabolism, and anti‐microbial proteins. Re‐sequencing of seven other genotypes confirmed low diversity and low heterozygosity within this endangered species. Important morphological characteristics of this species such as small tree size and high kernel recovery suggest that M. jansenii is an important source of these commercial traits for breeding. As a member of a small group of families that are sister to the core eudicots, this high‐quality genome also provides a key resource for evolutionary and comparative genomics studies.

Published
2021
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15. CGRP inhibits SARS-CoV-2 infection of bronchial epithelial cells and its pulmonary levels correlate with viral clearance in critical COVID-19 patients

Author

Barbosa Bomfim, Caio César, primary, Genin, Hugo, additional, Cottoignies-Callamarte, Andréa, additional, Gallois-Montbrun, Sarah, additional, Murigneux, Emilie, additional, Sams, Anette, additional, Rosenberg, Arielle R, additional, Belouzard, Sandrine, additional, Dubuisson, Jean, additional, Kosminder, Olivier, additional, Pène, Frédéric, additional, Terrier, Benjamin, additional, Bomsel, Morgane, additional, and Ganor, Yonatan, additional

Published
2024
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16. High-throughput multiplexed tandem repeat genotyping using targeted long-read sequencing [version 1; peer review: 1 approved with reservations, 1 not approved]

Author

Devika Ganesamoorthy, Mengjia Yan, Valentine Murigneux, Chenxi Zhou, Minh Duc Cao, Tania P. S. Duarte, and Lachlan J. M. Coin

Subjects
Research Article, Articles, Tandem repeats, targeted sequencing, long-read sequencing
Abstract

Background: Tandem repeats (TRs) are highly prone to variation in copy numbers due to their repetitive and unstable nature, which makes them a major source of genomic variation between individuals. However, population variation of TRs has not been widely explored due to the limitations of existing approaches, which are either low-throughput or restricted to a small subset of TRs. Here, we demonstrate a targeted sequencing approach combined with Nanopore sequencing to overcome these limitations. Methods: We selected 142 TR targets and enriched these regions using Agilent SureSelect target enrichment approach with only 200 ng of input DNA. We barcoded the enriched products and sequenced on Oxford Nanopore MinION sequencer. We used VNTRTyper and Tandem-genotypes to genotype TRs from long-read sequencing data. Gold standard PCR sizing analysis was used to validate genotyping results from targeted sequencing data. Results: We achieved an average of 3062-fold target enrichment on a panel of 142 TR loci, generating an average of 97X coverage per sample with 200 ng of input DNA per sample. We successfully genotyped an average of 75% targets and genotyping rate increased to 91% for the highest-coverage sample for targets with length less than 2 kb, and GC content greater than 25%. Alleles estimated from targeted long-read sequencing were concordant with gold standard PCR sizing analysis and highly correlated with alleles estimated from whole genome long-read sequencing. Conclusions: We demonstrate a targeted long-read sequencing approach that enables simultaneous analysis of hundreds of TRs and accuracy is comparable to PCR sizing analysis. Our approach is feasible to scale for more targets and more samples facilitating large-scale analysis of TRs.

Published
2020
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19. Assessing the potential of genetic resource introduction into elite germplasm: a collaborative multiparental population for Flint maize

Author

Sanchez, Dimitri, primary, Allier, Antoine, additional, Sadoun, Sarah Ben, additional, Tristan, Mary-Huard, additional, Bauland, Cyril, additional, Palaffre, Carine, additional, Lagardère, Bernard, additional, Madur, Delphine, additional, Combes, Valérie, additional, Melkior, Stephane, additional, Bettinger, Laurent, additional, Murigneux, Alain, additional, Moreau, Laurence, additional, and Charcosset, Alain, additional

Published
2023
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22. Breakage-Fusion-Bridge Events Trigger Complex Genome Rearrangements and Amplifications in Developmentally Arrested T Cell Lymphomas

Author

Joy J. Bianchi, Valentine Murigneux, Marie Bedora-Faure, Chloé Lescale, and Ludovic Deriano

Subjects
Biology (General), QH301-705.5
Abstract

Summary: To reveal the relative contribution of the recombination activating gene (RAG)1/2 nuclease to lymphomagenesis, we conducted a genome-wide analysis of T cell lymphomas from p53-deficient mice expressing or lacking RAG2. We found that while p53−/− lymphoblastic T cells harbor primarily ectopic DNA deletions, Rag2−/− p53−/− T cell lymphomas display complex genomic rearrangements associated with amplification of the chromosomal location 9qA4-5.3. We show that this amplicon is generated by breakage-fusion-bridge during mitosis and arises distinctly in T cell lymphomas originating from an early progenitor stage. Notably, we report amplification of the corresponding syntenic region (11q23) in a subset of human leukemia leading to the overexpression of several cancer genes, including MLL/KMT2A. Our findings provide direct evidence that lymphocytes undergo malignant transformation through distinct genome architectural routes that are determined by both RAG-dependent and RAG-independent DNA damage and a block in cell development. : Using p53-deficient T cell lymphoma mouse models, Bianchi et al. show that breakage-fusion-bridge events trigger complex focal genome rearrangements and amplifications in developmentally arrested lymphoblastic cells, leading to unique genome and transcriptome signatures found in some human hematological cancers. Keywords: cancer genome landscape, T cell development, T cell lymphoma, DNA damage, structural variation, breakage-fusion-bridge, RAG1/2 nuclease

Published
2019
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23. Epidermal mutation accumulation in photodamaged skin is associated with skin cancer burden and can be targeted through ablative therapy

Author

Ho Yi Wong, Ruby C. Lee, Sharene Chong, Stuti Kapadia, Michael Freeman, Valentine Murigneux, Susan Brown, H. Peter Soyer, Edwige Roy, and Kiarash Khosrotehrani

Subjects
Multidisciplinary
Abstract

The main carcinogen for keratinocyte skin cancers (KCs) such as basal and squamous cell carcinomas is ultraviolet (UV) radiation. There is growing evidence that accumulation of mutations and clonal expansion play a key role in KC development. The relationship between UV exposure, epidermal mutation load, and KCs remains unclear. Here, we examined the mutation load in both murine ( n = 23) and human ( n = 37) epidermal samples. Epidermal mutations accumulated in a UV dose–dependent manner, and this mutation load correlated with the KC burden. Epidermal ablation (either mechanical or laser induced), followed by spontaneous healing from underlying epithelial adnexae reduced the mutation load markedly in both mouse ( n = 8) and human ( n = 6) clinical trials. In a model of UV-induced basal cell carcinoma, epidermal ablation reduced incident lesions by >80% ( n = 5). Overall, our findings suggest that mutation burden is strongly associated with KC burden and represents a target to prevent subsequent KCs.

Published
2023
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27. 'Les composantes de l’ordre public, l’affaire des cirques avec animaux sauvages'

Author

Murigneux, Léa, Centre Michel de l'Hospital : laboratoire de recherche en sciences juridiques et politiques (CMH ), Université Clermont Auvergne (UCA), Léa Murigneux, doctorante en droit public, CMH UR 4232-UCA, Christophe Testard, Pr de droit public, CMH UR 4232-UCA, and ACDD Association clermontoise des doctorants et docteurs en droit

Subjects
[SHS.DROIT]Humanities and Social Sciences/Law
Abstract

National audience

Published
2022

28. Massive genome reduction occurred prior to the origin of coral algal symbionts

Author

Sarah Shah, Katherine E. Dougan, Yibi Chen, Rosalyn Lo, Gemma Laird, Michael D. A. Fortuin, Subash K. Rai, Valentine Murigneux, Anthony J. Bellantuono, Mauricio Rodriguez-Lanetty, Debashish Bhattacharya, and Cheong Xin Chan

Abstract

Dinoflagellates in the Family Symbiodiniaceae (Order Suessiales) are diverse, predominantly symbiotic lineages that associate with taxa such as corals and jellyfish. Their ancestor is believed to have been free-living, and the establishment of symbiosis (i.e., symbiogenesis) is hypothesised to have occurred multiple times during Symbiodiniaceae evolution. Among Symbiodiniaceae taxa, the genusEffreniumis an early diverging, free-living lineage that is phylogenetically positioned between two robustly supported groups of genera within which symbiotic taxa have emerged. The lack of symbiogenesis inEffreniumsuggests that the ancestral features of Symbiodiniaceae may have been retained in this lineage. Here we presentde novoassembled genomes and associated transcriptome data from three isolates ofEffrenium voratum. We compared theEffreniumgenomes (1.2-1.9 Gbp in size) and gene features with those of 16 Symbiodiniaceae taxa and other outgroup dinoflagellates. Surprisingly, we find that genome reduction, which is often associated with a symbiotic lifestyle, predates the origin of Symbiodiniaceae. We postulate that adaptation to an extreme habitat (e.g., as inPolarella glacialis) or life in oligotrophic conditions resulted in the Suessiales ancestor having a haploid genome size<2Gbp, which was retained (or reduced) among all extant algae in this lineage. Nonetheless, our data reveal that the free-living lifestyle distinguishesEffreniumfrom symbiotic Symbiodiniaceae vis-à-vis their longer introns, more-extensive mRNA editing, fewer (∼30%) lineage-specific gene families, and lower (∼10%) level of pseudogenisation. These results demonstrate how genome reduction and the adaptation to symbiotic versus free-living lifestyles intersect, and have driven the diversification and genome evolution of Symbiodiniaceae.

Published
2023
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29. Clonal hematopoiesis driven by chromosome 1q/MDM4 trisomy defines a canonical route toward leukemia in Fanconi anemia

Author

Marie Sebert, Stéphanie Gachet, Thierry Leblanc, Alix Rousseau, Olivier Bluteau, Rathana Kim, Raouf Ben Abdelali, Flore Sicre de Fontbrune, Loïc Maillard, Carèle Fedronie, Valentine Murigneux, Léa Bellenger, Naira Naouar, Samuel Quentin, Lucie Hernandez, Nadia Vasquez, Mélanie Da Costa, Pedro H. Prata, Lise Larcher, Marie de Tersant, Matthieu Duchmann, Anna Raimbault, Franck Trimoreau, Odile Fenneteau, Wendy Cuccuini, Nathalie Gachard, Nathalie Auger, Giulia Tueur, Maud Blanluet, Claude Gazin, Michèle Souyri, Francina Langa Vives, Aaron Mendez-Bermudez, Hélène Lapillonne, Etienne Lengline, Emmanuel Raffoux, Pierre Fenaux, Lionel Adès, Edouard Forcade, Charlotte Jubert, Carine Domenech, Marion Strullu, Bénédicte Bruno, Nimrod Buchbinder, Caroline Thomas, Arnaud Petit, Guy Leverger, Gérard Michel, Marina Cavazzana, Eliane Gluckman, Yves Bertrand, Nicolas Boissel, André Baruchel, Jean-Hugues Dalle, Emmanuelle Clappier, Eric Gilson, Ludovic Deriano, Sylvie Chevret, François Sigaux, Gérard Socié, Dominique Stoppa-Lyonnet, Hugues de Thé, Christophe Antoniewski, Dominique Bluteau, Régis Peffault de Latour, Jean Soulier, Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Génomes, biologie cellulaire et thérapeutiques (GenCellDi (U944 / UMR7212)), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), AP-HP Hôpital universitaire Robert-Debré [Paris], Recherche clinique appliquée à l'hématologie (URP_3518), Intégrité du génome, immunité et cancer - Genome integrity, Immunity and Cancer, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), CHU Limoges, Institut Gustave Roussy (IGR), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de Recherche en Génomique Humaine (CNRGH), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Hématopoïèse normale et pathologique : émergence, environnement et recherche translationnelle [Paris] ((UMR_S1131 / U1131)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center (CIGM), Institut Pasteur [Paris] (IP), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), CHU Nice [Cimiez], Hôpital Cimiez [Nice] (CHU), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpitaux universitaires Est parisien [AP-HP], CHU Bordeaux [Bordeaux], Hospices Civils de Lyon (HCL), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Rouen, Normandie Université (NU), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Hôpital de la Timone [CHU - APHM] (TIMONE), CIC NECKER BT (CIC 1416), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Collège de France (CdF (institution)), École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL), This study received support from the European Research Council (ERC) Consolidator Grant to J.S. (CEVAL-311660), the FP7 Eurofancolen program (HEALTH-F5-2012-305421), the ANR program PACRI (Projet alliance parisienne des instituts de recherche en cancérologie), the CONECT-AML (Collaborative Network for Children and Teenagers with Acute Myeloid Leukemia) program supported by a grant from the Institut National du Cancer (INCa), Fondation ARC, Ligue nationale contre le cancer, and Laurette Fugain (INCa-ARC-LIGUE_11905) to J.S. and C.A., and the Association Française pour la Maladie de Fanconi (AFMF) grants 'Histoire naturelle de la maladie de Fanconi' to R.P.L. and J.S., 'Modélisation de la transformation leucémique dans la maladie de Fanconi' to D.B., and 'Cribles fonctionnels à haut débit de gènes modificateurs de la maladie de Fanconi' to C.G. M.S. was supported by the AVIESAN-INCa Program 'Formation à la Recherche Translationnelle,' and A.R. by a grant from the Fondation ARC. The work in E.G.’s lab is supported by Fondation ARC and ANR Telochrom. The work in L.D.’s lab is supported by INCa (PLBIO16-181) and ERC (310917)., ANR-11-PHUC-0002,PACRI,Alliance Parisienne des Instituts de Recherche en Cancérologie(2011), European Project: 311660,EC:FP7:ERC,ERC-2012-StG_20111109,CEVAL(2013), and European Project: 305421,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EUROFANCOLEN(2013)

Subjects
MDM4, Fanconi anemia, precision medicine, [SDV]Life Sciences [q-bio], Genetics, leukemia, clonal hematopoiesis, Molecular Medicine, Cell Biology, TP53, mutational signature, genomic instability, BRCA2
Abstract

International audience; Fanconi anemia (FA) patients experience chromosome instability, yielding hematopoietic stem/progenitor cell (HSPC) exhaustion and predisposition to poor-prognosis myeloid leukemia. Based on a longitudinal cohort of 335 patients, we performed clinical, genomic, and functional studies in 62 patients with clonal evolution. We found a unique pattern of somatic structural variants and mutations that shares features of BRCA-related cancers, the FA-hallmark being unbalanced, microhomology-mediated translocations driving copy-number alterations. Half the patients developed chromosome 1q gain, driving clonal hematopoiesis through MDM4 trisomy downmodulating p53 signaling later followed by secondary acute myeloid lukemia genomic alterations. Functionally, MDM4 triplication conferred greater fitness to murine and human primary FA HSPCs, rescued inflammation-mediated bone marrow failure, and drove clonal dominance in FA mouse models, while targeting MDM4 impaired leukemia cells in vitro and in vivo. Our results identify a linear route toward secondary leukemogenesis whereby early MDM4-driven downregulation of basal p53 activation plays a pivotal role, opening monitoring and therapeutic prospects.

Published
2023
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30. The Dynamics of Interleukin-10-Afforded Protection during Dextran Sulfate Sodium-Induced Colitis

Author

Ana Cardoso, Antonio Gil Castro, Ana Catarina Martins, Guilhermina M. Carriche, Valentine Murigneux, Isabel Castro, Ana Cumano, Paulo Vieira, and Margarida Saraiva

Subjects
interleukin-10, macrophages, inflammation, colitis, therapy, Immunologic diseases. Allergy, RC581-607
Abstract

Inflammatory bowel disease encompasses a group of chronic-inflammatory conditions of the colon and small intestine. These conditions are characterized by exacerbated inflammation of the organ that greatly affects the quality of life of patients. Molecular mechanisms counteracting this hyperinflammatory status of the gut offer strategies for therapeutic intervention. Among these regulatory molecules is the anti-inflammatory cytokine interleukin (IL)-10, as shown in mice and humans. Indeed, IL-10 signaling, particularly in macrophages, is essential for intestinal homeostasis. We sought to investigate the temporal profile of IL-10-mediated protection during chemical colitis and which were the underlying mechanisms. Using a novel mouse model of inducible IL-10 overexpression (pMT-10), described here, we show that mice preconditioned with IL-10 for 8 days before dextran sulfate sodium (DSS) administration developed a milder colitic phenotype. In IL-10-induced colitic mice, Ly6C cells isolated from the lamina propria showed a decreased inflammatory profile. Because our mouse model leads to transcription of the IL-10 transgene in the bone marrow and elevated seric IL-10 concentration, we investigated whether IL-10 could imprint immune cells in a long-lasting way, thus conferring sustained protection to colitis. We show that this was not the case, as IL-10-afforded protection was only observed if IL-10 induction immediately preceded DSS-mediated colitis. Thus, despite the protection afforded by IL-10 in colitis, novel strategies are required, specifically to achieve long-lasting protection.

Published
2018
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33. Improvements in the sequencing and assembly of plant genomes

Author

Ardashir Kharabian Masouleh, Bader Alsubaie, Robert J Henry, Onkar Nath, Ibrahim S. Al-Mssallem, Neena Mitter, Agnelo Furtado, Valentine Murigneux, Priyanka Sharma, Othman Al-Dossary, Bruce Topp, and Gabriel Rodrigues Alves Margarido

Subjects
0106 biological sciences, 0303 health sciences, food.ingredient, Contig, Applied Mathematics, General Mathematics, food and beverages, QA75.5-76.95, Computational biology, Biology, Plant genomes, 01 natural sciences, Genome, DNA sequencing, 03 medical and health sciences, Data sequences, food, Macadamia jansenii, Electronic computers. Computer science, SOFTWARES, Nanopore sequencing, Genome size, 030304 developmental biology, 010606 plant biology & botany
Abstract

BackgroundAdvances in DNA sequencing have reduced the difficulty of sequencing and assembling plant genomes. A range of methods for long read sequencing and assembly have been recently compared and we now extend the earlier study and report a comparison with more recent methods.ResultsUpdated Oxford Nanopore Technology software supported improved assemblies. The use of more accurate sequences produced by repeated sequencing of the same molecule (PacBio HiFi) resulted in much less fragmented assembly of sequencing reads. The use of more data to give increased genome coverage resulted in longer contigs (higher N50) but reduced the total length of the assemblies and improved genome completeness (BUSCO). The original model species, Macadamia jansenii, a basal eudicot, was also compared with the 3 other Macadamia species and with avocado (Persea americana), a magnoliid, and jojoba (Simmondsia chinensis) a core eudicot. In these phylogenetically diverse angiosperms, increasing sequence data volumes also caused a highly linear increase in contig size, decreased assembly length and further improved already high completeness. Differences in genome size and sequence complexity apparently influenced the success of assembly from these different species.ConclusionsAdvances in long read sequencing technology have continued to significantly improve the results of sequencing and assembly of plant genomes. However, results were consistently improved by greater genome coverage (using an increased number of reads) with the amount needed to achieve a particular level of assembly being species dependant.

Published
2021
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35. Selection of Bis-Indolyl Pyridines and Triphenylamines as New Inhibitors of SARS-CoV-2 Cellular Entry by Modulating the Spike Protein/ACE2 Interfaces

Author

Lapaillerie, Delphine, primary, Charlier, Cathy, additional, Guyonnet-Dupérat, Véronique, additional, Murigneux, Emilie, additional, Fernandes, Henrique S., additional, Martins, Fábio G., additional, Magalhães, Rita P., additional, Vieira, Tatiana F., additional, Richetta, Clémence, additional, Subra, Frédéric, additional, Lebourgeois, Samuel, additional, Charpentier, Charlotte, additional, Descamps, Diane, additional, Visseaux, Benoît, additional, Weigel, Pierre, additional, Favereaux, Alexandre, additional, Beauvineau, Claire, additional, Buron, Frédéric, additional, Teulade-Fichou, Marie-Paule, additional, Routier, Sylvain, additional, Gallois-Montbrun, Sarah, additional, Meertens, Laurent, additional, Delelis, Olivier, additional, Sousa, Sérgio F., additional, and Parissi, Vincent, additional

Published
2022
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38. Selection of Bis-Indolyl Pyridines and Triphenylamines as New Inhibitors of SARS-CoV-2 Cellular Entry by Modulating the Spike Protein/ACE2 Interfaces

Author

Delphine Lapaillerie, Cathy Charlier, Véronique Guyonnet-Dupérat, Emilie Murigneux, Henrique S. Fernandes, Fábio G. Martins, Rita P. Magalhães, Tatiana F. Vieira, Clémence Richetta, Frédéric Subra, Samuel Lebourgeois, Charlotte Charpentier, Diane Descamps, Benoît Visseaux, Pierre Weigel, Alexandre Favereaux, Claire Beauvineau, Frédéric Buron, Marie-Paule Teulade-Fichou, Sylvain Routier, Sarah Gallois-Montbrun, Laurent Meertens, Olivier Delelis, Sérgio F. Sousa, Vincent Parissi, Microbiologie Fondamentale et Pathogénicité (MFP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Unité en Sciences Biologiques et Biotechnologies de Nantes (US2B), Centre National de la Recherche Scientifique (CNRS)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), TBM-Core [Bordeaux] (UMS3427 - INSERM US005), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Universidade do Porto = University of Porto, Laboratoire de biologie et pharmacologie appliquée (LBPA), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, Interdisciplinary Institute for Neuroscience [Bordeaux] (IINS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Chimie et modélisation pour la biologie du cancer (CMBC), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité en Sciences Biologiques et Biotechnologies de Nantes - UMR CNRS 6286 (US2B), Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005), and delelis, olivier

Subjects
[SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Pharmacology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Pyridines, SARS-CoV-2, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, ACE2, COVID-19, spike, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Peptidyl-Dipeptidase A, Virus Internalization, COVID-19 Drug Treatment, inhibitor, Molecular Docking Simulation, Infectious Diseases, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Spike Glycoprotein, Coronavirus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Humans, Pharmacology (medical), viral entry, Angiotensin-Converting Enzyme 2, Protein Binding
Abstract

International audience; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the infectious agent that has caused the current coronavirus disease (COVID) pandemic. Viral infection relies on the viral S (spike) protein/cellular receptor ACE2 interaction. Disrupting this interaction would lead to early blockage of viral replication. To identify chemical tools to further study these functional interfaces, 139,146 compounds from different chemical libraries were screened through an S/ACE2 in silico virtual molecular model. The best compounds were selected for further characterization using both cellular and biochemical approaches, reiterating SARS-CoV-2 entry and the S/ACE2 interaction. We report here two selected hits, bis-indolyl pyridine AB-00011778 and triphenylamine AB-00047476. Both of these compounds can block the infectivity of lentiviral vectors pseudotyped with the SARS-CoV-2 S protein as well as wild-type and circulating variant SARS-CoV-2 strains in various human cell lines, including pulmonary cells naturally susceptible to infection. AlphaLISA and biolayer interferometry confirmed a direct inhibitory effect of these drugs on the S/ACE2 association. A specific study of the AB-00011778 inhibitory properties showed that this drug inhibits viral replication with a 50% effective concentration (EC 50) between 0.1 and 0.5 mM depending on the cell lines. Molecular docking calculations of the interaction parameters of the molecules within the S/ACE2 complex from both wild-type and circulating variants of the virus showed that the molecules may target multiple sites within the S/ACE2 interface. Our work indicates that AB-00011778 constitutes a good tool for modulating this interface and a strong lead compound for further therapeutic purposes.

Published
2022
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41. Genetic aberrations of NLRC5 are associated with downregulated MHC‐I antigen presentation and impaired T‐cell immunity in follicular lymphoma

Author

Lilia Merida de Long, Simone Birch, Valentine Murigneux, Justina Lee, Maher K. Gandhi, Karolina Bednarska, Joshua W.D. Tobin, Jay Gunawardana, and Muhammed B. Sabdia

Subjects
biology, business.industry, medicine.medical_treatment, Antigen presentation, Follicular lymphoma, Impaired T cell immunity, Immunotherapy, Gene deletion, medicine.disease, NLRC5, Immunology, MHC class I, biology.protein, Medicine, business
Published
2020
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49. Two Cytosolic Glutamine Synthetase Isoforms of Maize Are Specifically Involved in the Control of Grain Production

Author

Martin, Antoine, Lee, Judy, Kichey, Thomas, Gerentes, Denise, Zivy, Michel, Tatout, Christophe, Dubois, Frédéric, Balliau, Thierry, Valot, Benoît, Davanture, Marlène, Tercé-Laforgue, Thérèse, Quilleré, Isabelle, Coque, Marie, Gallais, André, Gonzalez-Moro, María-Begoña, Bethencourt, Linda, Habash, Dimah Z., Lea, Peter J., Charcosset, Alain, Perez, Pascual, Murigneux, Alain, Sakakibara, Hitoshi, Edwards, Keith J., and Hirel, Bertrand

Published
2006
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