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44 results on '"Lefort, Nathalie"'

1. Engineering 3D micro-compartments for highly efficient and scale-independent expansion of human pluripotent stem cells in bioreactors

Author

Cohen, Philippe J.R., Luquet, Elisa, Pletenka, Justine, Leonard, Andrea, Warter, Elise, Gurchenkov, Basile, Carrere, Jessica, Rieu, Clément, Hardouin, Jerome, Moncaubeig, Fabien, Lanero, Michael, Quelennec, Eddy, Wurtz, Helene, Jamet, Emilie, Demarco, Maelle, Banal, Celine, Van Liedekerke, Paul, Nassoy, Pierre, Feyeux, Maxime, Lefort, Nathalie, and Alessandri, Kevin

Published
2023
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3. UNC45A deficiency causes microvillus inclusion disease-like phenotype by impairing myosin VB-dependent apical trafficking

Author

Duclaux-Loras, Remi, Lebreton, Corinne, Berthelet, Jeremy, Charbit-Henrion, Fabienne, Nicolle, Ophelie, de Courtils, Celine Revenu, Waich, Stephanie, Valovka, Taras, Khiat, Anis, Rabant, Marion, Racine, Caroline, Guerrera, Ida Chiara, Baptista, Julia, Mahe, Maxime M., Hess, Michael W., Durel, Beatrice, Lefort, Nathalie, Banal, Celine, Parisot, Melanie, Talbotec, Cecile, Lacaille, Florence, Ecochard-Dugelay, Emmanuelle, Demir, Arzu Meltem, Vogel, Georg F., Faivre, Laurence, Rodrigues, Astor, Fowler, Darren, Janecke, Andreas R., Muller, Thomas, Huber, Lukas A., Rodrigues-Lima, Fernando, Ruemmele, Frank M., Uhlig, Holm H., Del Bene, Filippo, Michaux, Gregoire, Cerf-Bensussan, Nadine, and Parlato, Marianna

Subjects
Gene mutations -- Research, Genetic disorders -- Causes of, Medical research, Medicine, Experimental, Myosin -- Genetic aspects -- Health aspects, Diarrhea -- Genetic aspects -- Causes of, Molecular chaperones -- Genetic aspects -- Health aspects, Cell membranes -- Health aspects, Phenotype -- Research, Health care industry
Abstract

Variants in the UNC45A cochaperone have been recently associated with a syndrome combining diarrhea, cholestasis, deafness, and bone fragility. Yet the mechanism underlying intestinal failure in UNC45A deficiency remains unclear. Here, biallelic variants in UNC45A were identified by next-generation sequencing in 6 patients with congenital diarrhea. Corroborating in silico prediction, variants either abolished UNC45A expression or altered protein conformation. Myosin VB was identified by mass spectrometry as client of the UNC45A chaperone and was found misfolded in [UNC45A.sup.KO] Caco-2 cells. In keeping with impaired myosin VB function, [UNC45A.sup.KO] Caco-2 cells showed abnormal epithelial morphogenesis that was restored by full-length UNC45A, but not by mutant alleles. Patients and [UNC45A.sup.KO] 3D organoids displayed altered luminal development and microvillus inclusions, while 2D cultures revealed Rab11 and apical transporter mislocalization as well as sparse and disorganized microvilli. All those features resembled the subcellular abnormalities observed in duodenal biopsies from patients with microvillus inclusion disease. Finally, microvillus inclusions and shortened microvilli were evidenced in enterocytes from unc45a-deficient zebrafish. Taken together, our results provide evidence that UNC45A plays an essential role in epithelial morphogenesis through its cochaperone function of myosin VB and that UNC45A loss causes a variant of microvillus inclusion disease., Introduction Congenital diarrhea disorders (CDDs) are rare monogenic diseases characterized by chronic, life-threatening diarrhea starting early in life (1, 2). Depending on the mechanism, diarrhea can be the only symptom [...]

Published
2022
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4. MINPP1 prevents intracellular accumulation of the chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia

Author

Ucuncu, Ekin, Rajamani, Karthyayani, Wilson, Miranda S. C., Medina-Cano, Daniel, Altin, Nami, David, Pierre, Barcia, Giulia, Lefort, Nathalie, Banal, Céline, Vasilache-Dangles, Marie-Thérèse, Pitelet, Gaële, Lorino, Elsa, Rabasse, Nathalie, Bieth, Eric, Zaki, Maha S., Topcu, Meral, Sonmez, Fatma Mujgan, Musaev, Damir, Stanley, Valentina, Bole-Feysot, Christine, Nitschké, Patrick, Munnich, Arnold, Bahi-Buisson, Nadia, Fossoud, Catherine, Giuliano, Fabienne, Colleaux, Laurence, Burglen, Lydie, Gleeson, Joseph G., Boddaert, Nathalie, Saiardi, Adolfo, and Cantagrel, Vincent

Published
2020
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10. 2D and 3D Human Induced Pluripotent Stem Cell-Based Models to Dissect Primary Cilium Involvement during Neocortical Development

Author

Boutaud, Lucile, primary, Michael, Marie, primary, Banal, Céline, primary, Calderon, Damelys, primary, Farcy, Sarah, primary, Pernelle, Julie, primary, Goudin, Nicolas, primary, Maillard, Camille, primary, Dimartino, Clémantine, primary, Deleschaux, Cécile, primary, Dupichaud, Sébastien, primary, Lebreton, Corinne, primary, Saunier, Sophie, primary, Attié-Bitach, Tania, primary, Bahi-Buisson, Nadia, primary, Lefort, Nathalie, primary, and Thomas, Sophie, primary

Published
2022
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13. C-STEM: ENGINEERING NICHE-LIKE MICRO-COMPARTMENTS FOR OPTIMAL AND SCALE-INDEPENDENT EXPANSION OF HUMAN PLURIPOTENT STEM CELLS IN BIOREACTORS

Author

Cohen, Philippe J.R., primary, Luquet, Elisa, additional, Pletenka, Justine, additional, Leonard, Andrea, additional, Warter, Elise, additional, Gurchenkov, Basile, additional, Carrere, Jessica, additional, Rieu, Clement, additional, Hardouin, Jerome, additional, Moncaubeig, Fabien, additional, Lanero, Michael, additional, Quelennec, Eddy, additional, Wurtz, Helene, additional, Jamet, Emilie, additional, Demarco, Maelle, additional, banal, Celine, additional, Van Liedekerke, Paul, additional, Nassoy, Pierre, additional, Feyeux, Maxime, additional, Lefort, Nathalie, additional, and Alessandri, kevin, additional

Published
2021
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14. Recurrent genomic instability of chromosome 1q in neural derivatives of human embryonic stem cells

Author

Varela, Christine, Denis, Jerome Alexandre, Polentes, Jerome, Feyeux, Maxime, Aubert, Sophie, Champon, Benoite, Pietu, Genevieve, Peschanski, Marc, and Lefort, Nathalie

Subjects
Gene mutations -- Health aspects, Embryonic stem cells -- Physiological aspects -- Genetic aspects -- Research, Chromosomal instability syndromes -- Risk factors -- Research, Health care industry
Abstract

Human pluripotent stem cells offer a limitless source of cells for regenerative medicine. Neural derivatives of human embryonic stem cells (hESCs) are currently being used for cell therapy in 3 clinical trials. However, hESCs are prone to genomic instability, which could limit their clinical utility. Here, we report that neural differentiation of hESCs systematically produced a neural stem cell population that could be propagated for more than 50 passages without entering senescence; this was true for all 6 hESC lines tested. The apparent spontaneous loss of evolution toward normal senescence of somatic cells was associated with a jumping translocation of chromosome 1q. This chromosomal defect has previously been associated with hematologic malignancies and pediatric brain tumors with poor clinical outcome. Neural stem cells carrying the 1q defect implanted into the brains of rats failed to integrate and expand, whereas normal cells engrafted. Our results call for additional quality controls to be implemented to ensure genomic integrity not only of undifferentiated pluripotent stem cells, but also of hESC derivatives that form cell therapy end products, particularly neural lines., Introduction Whether pluripotent stem cell derivatives can eventually be used widely for therapeutic purpose after the first ongoing clinical trials (1-4) will depend upon their capacity to pass strict quality [...]

Published
2012
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18. Generation of an iPSC line (IMAGINi022-A) from a patient carrying a SOX10 missense mutation and presenting with deafness, depigmentation and progressive neurological impairment

Author

Banal, Celine, primary, Quelennec, Eddy, additional, Bertani-Torres, William, additional, Gacem, Nadjet, additional, Amiel, Jeanne, additional, Marlin, Sandrine, additional, Petit, Florence, additional, Pingault, Veronique, additional, Lefort, Nathalie, additional, and Bondurand, Nadege, additional

Published
2020
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20. MINPP1prevents intracellular accumulation of the cation chelator inositol hexakisphosphate and is mutated in Pontocerebellar Hypoplasia

Author

Ucuncu, Ekin, primary, Rajamani, Karthyayani, additional, Wilson, Miranda S.C., additional, Medina-Cano, Daniel, additional, Altin, Nami, additional, David, Pierre, additional, Barcia, Giulia, additional, Lefort, Nathalie, additional, Vasilache-Dangles, Marie-Thérèse, additional, Pitelet, Gaële, additional, Lorino, Elsa, additional, Rabasse, Nathalie, additional, Bieth, Eric, additional, Zaki, Maha S., additional, Topcu, Meral, additional, Sonmez, Fatma Mujgan, additional, Musaev, Damir, additional, Stanley, Valentina, additional, Bole-Feysot, Christine, additional, Nitschké, Patrick, additional, Munnich, Arnold, additional, Bahi-Buisson, Nadia, additional, Fossoud, Catherine, additional, Giuliano, Fabienne, additional, Colleaux, Laurence, additional, Burglen, Lydie, additional, Gleeson, Joseph G., additional, Boddaert, Nathalie, additional, Saiardi, Adolfo, additional, and Cantagrel, Vincent, additional

Published
2020
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22. Fetal bovine serum impacts the observed N‐glycosylation defects in TMEM165 KO HEK cells

Author

Climer, Leslie, Morelle, Willy, De Bettignies, Geoffroy, Krzewinski Recchi, Marie-Ange, Lupashin, Vladimir, Medina-Cano, Daniel, Ucuncu, Ekin, Nguyen, Lam Son, Nicouleau, Michael, Lipecka, Joanna, Bizot, Jean-Charles, Thiel, Christian, Lefort, Nathalie, Faivre-Sarrailh, Catherine, Colleaux, Laurence, Guerrera, Ida Chiara, Cantagrel, Vincent, Lebredonchel, Elodie, Garat, Anne, Legrand, Dominique, Decool, Valérie, Klein, André, Ouzzine, Mohamed, Gasnier, Bruno, Potelle, Sven, Groux‐Degroote, Sophie, Cogez, Virginie, Noel, Maxence, Portier, Lucie, Solórzano, Carlos, Dall'Olio, Fabio, Steenackers, Agata, Mortuaire, Marlène, Gonzalez‐Pisfil, Mariano, Henry, Mélanie, Heliot, Laurent, Harduin-Lepers, Anne, Berthe, Audrey, Zaffino, Marie, Muller, claire, Houdou, Marine, Schulz, Céline, Bost, Frédéric, De Fay, Elia, Mazerbourg, Sabine, Flament, Stéphane, Mouajjah, Dounia, Ashikov, Angel, Abu Bakar, Nurulamin, Wen, Xiao-Yan, Niemeijer, Marco, Rodrigues Pinto Osorio, Glentino, Brand-Arzamendi, Koroboshka, Hasadsri, Linda, Hansikova, Hana, Raymond, Kimiyo, Ondruskova, Nina, Simon, Marleen, Pfundt, Rolph, Timal, Sharita, Beumers, Roel, Smeets, Roel, Kersten, Marjan, Huijben, Karin, Linders, Peter, van den Bogaart, Geert, van Hijum, Sacha, Rodenburg, Richard, van den Heuvel, Lambertus, Van Spronsen, Francjan, Honzik, Tomas, van Scherpenzeel, Monique, Lefeber, Dirk, Mirjam, Wamelink, Han, Brunner, Helen, Mundy, Helen, Michelakakis, Peter, van Hasselt, Jiddeke, van de Kamp, Diego, Martinelli, Lars, Morkrid, Katja, Brocke Holmefjord, Jozef, Hertecant, Majid, Alfadhel, Kevin, Carpenter, Johann, te Water Naude, Delos, Maxime, Hellec, Charles, Fifre, Alexandre, Carpentier, Mathieu, Papy-Garcia, Dulce, Allain, Fabrice, Denys, Agnés, Gilormini, Pierre André, Lion, Cédric, Vicogne, Dorothée, Guerardel, Yann, Biot, Christophe, Witters, Peter, Breckpot, Jeroen, Preston, Graem, Morava, Eva, Rujano, Maria, Cannata Serio, Magda, Panasyuk, Ganna, Reunert, Janine, Hauser, Virginie, Park, Julien, Freisinger, Peter, Guida, Maria Clara, Maier, Esther, Wada, Yoshinao, Jäger, Stefanie, Krogan, Nevan, Kretz, Oliver, Nobre, Susana, Garcia, Paula, Quelhas, Dulce, Bird, Thomas, Raskind, Wendy, Schwake, Michael, Duvet, Sandrine, Marquardt, Thorsten, Simons, Matias, Blommaert, Eline, Péanne, Romain, Cherepanova, Natalia, Rymen, Daisy, Staels, Frederik, Jaeken, Jaak, Race, Valérie, Keldermans, Liesbeth, Souche, Erika, Corveleyn, Anniek, Sparkes, Rebecca, Bhattacharya, Kaustuv, Devalck, Christine, Schrijvers, Rik, Foulquier, Francois, Gilmore, Reid, Matthijs, Gert, Université Lille Nord de France (COMUE), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Variabilité génétique des défenses de l'organisme face à son environnement chimique, PRES Université Lille Nord de France-Université de Lille, Droit et Santé, ANR-15-CE14-0001,SOLV_CDG,Décryptage des patients CDG (Congenital Disorders of Glyvosylation) déficients en TMEM165 - de la compréhension des mécanismes moléculaires à une thérapie(2015), ANR-15-RAR3-0004,EURO-CDG-2,A European research network directed towards improving diagnosis and treatment of inborn glycosylation disorders.(2015), European Project: 643578,H2020,H2020-HCO-2014,E-Rare-3(2014), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS], Baylor University, University of Arkansas for Medical Sciences [UAMS], Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Key-Obs, JRC Institute for Energy and Transport (IET), European Commission - Joint Research Centre [Petten], Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Impact de l'environnement chimique sur la santé humaine (IMPECS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Biologie cellulaire et moléculaire de la sécrétion (BCMS), Centre National de la Recherche Scientifique (CNRS), Departamento de Bioquímica, Instituto Nacional de Enfermedades Respiratorias, Department of Experimental, Diagnostic and Specialty Medicine (DIMES) (DIMES), Università di Bologna [Bologna] (UNIBO), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Biophotonique Cellulaire Fonctionelle, Institut de Recherche Interdisciplinaire, Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medicine & Physiology , University of Toronto, First Faculty of Medicine, Charles University [Prague], University Medical Center [Utrecht], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Paediatrics, Beatrix Children's Hospital/University Medical Center Groningen, Université Toulouse 1 Capitole (UT1), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Chimie Moléculaire et Formulation (EA 4478), Université de Lille, Sciences et Technologies, Unité de Catalyse et de Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Ecole Centrale de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Pediatrics, University Children's Hospital, Centre de recherche Croissance et signalisation (UMR_S 845), Reutlingen University, Department of General Pediatrics, Münster University Children Hospital, Molecular Diagnostics, Center for Human Genetics, Gasthuisberg, Katholieke Universiteit Leuven and Flanders Interuniversity Institute for Biotechnology 4, Leuven, Belgium, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Center for Human Genetics, and Laboratory of clinical immunology

Subjects
Glycosylation, Protein family, [SDV]Life Sciences [q-bio], Golgi Apparatus, FBS, manganese level, N‐glycosylation defects, TMEM165, Article, Antiporters, Glycomics, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, Congenital Disorders of Glycosylation, 0302 clinical medicine, N-linked glycosylation, Genetics, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cation Transport Proteins, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Manganese, 0303 health sciences, Ion Transport, HEK 293 cells, Serum Albumin, Bovine, Golgi apparatus, Embryonic stem cell, Cell biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], carbohydrates (lipids), HEK293 Cells, chemistry, symbols, Calcium, 030217 neurology & neurosurgery, Fetal bovine serum
Abstract

TMEM165 is involved in a rare genetic human disease named TMEM165‐CDG (congenital disorders of glycosylation). It is Golgi localized, highly conserved through evolution and belongs to the uncharacterized protein family 0016 (UPF0016). The use of isogenic TMEM165 KO HEK cells was crucial in deciphering the function of TMEM165 in Golgi manganese homeostasis. Manganese is a major cofactor of many glycosylation enzymes. Severe Golgi glycosylation defects are observed in TMEM165 Knock Out Human Embryonic Kidney (KO HEK) cells and are rescued by exogenous manganese supplementation. Intriguingly, we demonstrate in this study that the observed Golgi glycosylation defect mainly depends on fetal bovine serum, particularly its manganese level. Our results also demonstrate that iron and/or galactose can modulate the observed glycosylation defects in TMEM165 KO HEK cells. While isogenic cultured cells are widely used to study the impact of gene defects on proteins' glycosylation patterns, these results emphasize the importance of the use of validated fetal bovine serum in glycomics studies. 43;2

Published
2019

23. High N-glycan multiplicity is critical for neuronal adhesion and sensitizes the developing cerebellum to N-glycosylation defect

Author

Medina-Cano, Daniel, Ucuncu, Ekin, Nguyen, Lam Son, Nicouleau, Michael, Lipecka, Joanna, Bizot, Jean-Charles, Thiel, Christian, Foulquier, François, Lefort, Nathalie, Faivre-Sarrailh, Catherine, Colleaux, Laurence, Guerrera, Ida Chiara, Cantagrel, Vincent, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de chimie et procédés pour l'énergie, l'environnement et la santé (ICPEES), Université de Strasbourg (UNISTRA)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), JRC Institute for Energy and Transport (IET), European Commission - Joint Research Centre [Petten], Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), PRA, Fanny, Mécanismes développementaux des anomalies structurelles cérébelleuses - - SCD-Mec2016 - ANR-16-CE12-0005 - AAPG2016 - VALID, ERA-NET rare disease research implementing IRDiRC objectives - E-Rare-3 - - H20202014-12-01 - 2019-11-30 - 643578 - VALID, Institut de psychiatrie et neurosciences (U894 / UMS 1266), Key-Obs, ANR-16-CE12-0005,SCD-Mec,Mécanismes développementaux des anomalies structurelles cérébelleuses(2016), European Project: 643578,H2020,H2020-HCO-2014,E-Rare-3(2014), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Lille, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Sorbonne Paris Cité (USPC), and Centre de Psychiatrie et Neurosciences (U894)

Subjects
Glycosylation, MESH: Immunoglobulins, [SDV]Life Sciences [q-bio], MESH: Neurons, N-glycosylation, MESH: Unfolded Protein Response, MESH: Mice, Knockout, neuroscience, Purkinje Cells, MESH: Axon Guidance, Neural Pathways, cell biology, MESH: Animals, Biology (General), Mice, Knockout, Neurons, neuronal migration, MESH: Proteomics, Srd5a3, Cell Differentiation, MESH: Glycosylation, MESH: Motor Activity, Axon Guidance, MESH: Reproducibility of Results, MESH: Cell Adhesion Molecules, Medicine, lipids (amino acids, peptides, and proteins), [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH: Membrane Proteins, Research Article, MESH: Cell Differentiation, MESH: Mutation, animal structures, cerebellum, QH301-705.5, Science, Induced Pluripotent Stem Cells, Immunoglobulins, MESH: Cytoplasmic Granules, Motor Activity, MESH: Induced Pluripotent Stem Cells, Cytoplasmic Granules, MESH: 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, MESH: Cell Adhesion, MESH: Purkinje Cells, proteomics, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase, Polysaccharides, Animals, human, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], mouse, MESH: Neural Pathways, Cell Membrane, Membrane Proteins, Reproducibility of Results, cell adhesion, MESH: Cerebellum, carbohydrates (lipids), MESH: Polysaccharides, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH: Gene Deletion, Protein N-glycosylation, Mutation, Unfolded Protein Response, Cell Adhesion Molecules, Gene Deletion, MESH: Cell Membrane, congenital disorders of glycosylation
Abstract

International audience; Proper brain development relies highly on protein N-glycosylation to sustain neuronal migration, axon guidance and synaptic physiology. Impairing the N-glycosylation pathway at early steps produces broad neurological symptoms identified in congenital disorders of glycosylation. However, little is known about the molecular mechanisms underlying these defects. We generated a cerebellum specific knockout mouse for Srd5a3, a gene involved in the initiation of N-glycosylation. In addition to motor coordination defects and abnormal granule cell development, Srd5a3 deletion causes mild N-glycosylation impairment without significantly altering ER homeostasis. Using proteomic approaches, we identified that Srd5a3 loss affects a subset of glycoproteins with high N-glycans multiplicity per protein and decreased protein abundance or N-glycosylation level. As IgSF-CAM adhesion proteins are critical for neuron adhesion and highly N-glycosylated, we observed impaired IgSF-CAM-mediated neurite outgrowth and axon guidance in Srd5a3 mutant cerebellum. Our results link high N-glycan multiplicity to fine-tuned neural cell adhesion during mammalian brain development.

Published
2018

24. Caloric restriction increases lifespan but affects brain integrity in grey mouse lemur primates

Author

Pifferi, Fabien, Terrien, Jérémy, Marchal, Marc, Dal-Pan, Alexandre, Djelti, Fathia, Hardy, Isabelle, Chahory, Sabine, Cordonnier-Lefort, Nathalie, Desquilbet, Loic, Hurion, Murielle, Zahariev, Alexandre, Chery, Isabelle, Zizzari, Philippe, Perret, Martine, Epelbaum, Jacques, Blanc, Stéphane, Picq, Jean-Luc, Dhenain, Marc, Aujard, Fabienne, Mécanismes adaptatifs : des organismes aux communautés (MECADEV), Centre National de la Recherche Scientifique (CNRS)-Muséum national d'Histoire naturelle (MNHN), École nationale vétérinaire d'Alfort (ENVA), Ecole Nationale Vétérinaire d’Alfort, Unité d’anatomie pathologique, Université Paris-Est (UPE), Département Ecologie, Physiologie et Ethologie (DEPE-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Psychopathologie et Neuropsychologie (LPN), Université Paris 8 Vincennes-Saint-Denis (UP8), Laboratoire des Maladies Neurodégénératives - UMR 9199 (LMN), Service MIRCEN (MIRCEN), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Mécanismes Adaptatifs et Evolution (MECADEV), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Service MIRCEN (MIRCEN), Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Université Paris-Sud - Paris 11 (UP11)-Service MIRCEN (MIRCEN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), École nationale vétérinaire - Alfort (ENVA), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Centre de Psychiatrie et Neurosciences (U894), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
lcsh:Biology (General), [SDE]Environmental Sciences, lcsh:QH301-705.5
Abstract

International audience; The health benefits of chronic caloric restriction resulting in lifespan extension are wellestablished in many short-lived species, but the effects in humans and other primates remaincontroversial. Here we report the most advanced survival data and the associated follow-upto our knowledge of age-related alterations in a cohort of grey mouse lemurs (Microcebusmurinus, lemurid primate) exposed to a chronic moderate (30%) caloric restriction. Comparedto control animals, caloric restriction extended lifespan by 50% (from 6.4 to 9.6 years,median survival), reduced aging-associated diseases and preserved loss of brain white matterin several brain regions. However, caloric restriction accelerated loss of grey matterthroughout much of the cerebrum. Cognitive and behavioural performances were, however,not modulated by caloric restriction. Thus chronic moderate caloric restriction can extendlifespan and enhance health of a primate, but it affects brain grey matter integrity withoutaffecting cognitive performances.

Published
2018

26. Author response: High N-glycan multiplicity is critical for neuronal adhesion and sensitizes the developing cerebellum to N-glycosylation defect

Author

Medina-Cano, Daniel, primary, Ucuncu, Ekin, additional, Nguyen, Lam Son, additional, Nicouleau, Michael, additional, Lipecka, Joanna, additional, Bizot, Jean-Charles, additional, Thiel, Christian, additional, Foulquier, François, additional, Lefort, Nathalie, additional, Faivre-Sarrailh, Catherine, additional, Colleaux, Laurence, additional, Guerrera, Ida Chiara, additional, and Cantagrel, Vincent, additional

Published
2018
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27. Pathways to antigen expression after oral delivery of an Adenovirus-based vaccine

Author

Revaud, Julien, Unterfinger, Yves, Lacour, Sandrine, Rol, Nicolas, Suleman, Muhammad, Galea, Sandra, Versillé, Nicolas, Cordonnier-Lefort, Nathalie, Klonjkowski, Bernard, Corthésy, Blaise, Ben Arous, Juliette, Richardson, Jennifer, Virologie UMR1161 (VIRO), and Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

28. Pathways to antigen expression after oral delivery of an Adenovirus-based vaccine

Author

Revaud, Julien, Rol, Nicolas, Unterfinger, Yves, Maye, Jennifer, Galea, Sandra, Versillé, Nicolas, Cordonnier-Lefort, Nathalie, Klonjkowski, Bernard, Corthésy, Blaise, Ben Arous, Juliette, Richardson, Jennifer, Virologie UMR1161 (VIRO), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), Society for Mucosal Immunology. USA., and École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015

29. Etude des étapes précoces impliquées dans la mise en place de la réponse immunitaire suite à une vaccination par voie orale avec des vaccins vectorisés dérivés des adénovirus

Author

Revaud, Julien, Rol, Nicolas, Unterfinger, Yves, Maye, Jennifer, Versillé, Nicolas, Cordonnier-Lefort, Nathalie, Klonjkowski, Bernard, Corthésy, Blaise, Ben Arous, Juliette, Richardson, Jennifer, Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), and Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2015

30. Schmallenberg virus experimental infection on pregant goats

Author

LALOY, Eve, Cordonnier-Lefort, Nathalie, Bréard, Emmanuel, Trapp, Sascha, Riou, Mickaël, Ponsart, C., Pozzi, N., Hebert, T., Zientara, Stephan, Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Plateforme d'Infectiologie Expérimentale (PFIE), Institut National de la Recherche Agronomique (INRA), Laboratoire National de Contrôle des Reproducteurs (LNCR), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire d'Alfort (ENVA), UR Infectiologie animale et Santé publique (UR IASP), Plateforme d'Infectiologie Expérimentale (PFIE - INRA UE 1277), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), and Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT)

Subjects
[SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT]
Abstract

Présentations ESVP/ECVP; absent

Published
2014

31. Evidence of trans-placental transmission odf Bluetongue virus serotype 8 in goats

Author

Breard, Emmanuel, Cordonnier-Lefort, Nathalie, Zientara, Stephan, Sailleau, Corinne, Viarouge, Cyril, Millemann, Yves, Virologie UMR1161 (VIRO), Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-École nationale vétérinaire d'Alfort (ENVA), ONIRIS-INRA - Umr 1300 Bioagression, Epidémiologie et Analyse de Risque, Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Pathologie du Bétail, École nationale vétérinaire d'Alfort (ENVA), European College of Small Ruminant Health Management. Labo/service de l'auteur, INT., and École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)

Subjects
serotype 8, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, virus, Bluetongue, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2011

32. Encephalomyocarditis virus mortality in semi-wild bonobos (Pan panicus)

Author

Jones, P., Cordonnier-Lefort, Nathalie, Mahamba, C., Burt, F.J., Rakotovao, F., Swanepoel, R., Andre, C., Dauger, S., Bakkali, Labib, University College of London [London] (UCL), École nationale vétérinaire d'Alfort (ENVA), Sanctuaire Lola ya Bonobo, Les Petites Chutes de la Lukaya, Kimwenza, Mont Ngafula, Partenaires INRAE, University of the Free State, National Institute for Communicable Diseases [Johannesburg] (NICD), AP-HP Hôpital universitaire Robert-Debré [Paris], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
viruses, [SDV.BA]Life Sciences [q-bio]/Animal biology, bonobo, non-human primate, myocarditis, encephalomyocarditis virus, mortality
Abstract

International audience; Background Fatal myocarditis from encephalomyocarditis virus (EMCV)infection has previously been identified in sporadic and epidemic forms inmany species of captive non-human primates probably including one bonobo(Pan paniscus).Methods We investigated the deaths of two bonobos that were suspiciousof EMCV using a combination of histopathology, immunohistochemistryand, for one of the two bonobos, reverse transcription PCR.Results Histopathological examination of heart tissue from the two bonobosshowed changes characteristic of EMCV. Immunohistochemical studiesconfirmed the presence of EMCV antigen in heart tissue of both and inkidney and intestine of one of the bonobos. EMCV RNA was also isolatedfrom the serum of the bonobo tested.Conclusion Together, these findings confirm that EMCV was responsiblefor deaths of the two bonobos. Strict separation of bonobos in particularand captive primates in general from potential sources of EMCV contaminationshould be maintained to prevent mortality caused by EMCV.

Published
2011

37. Involvement of Mitochondrial Complex II Defects in Neuronal Death Produced by N-Terminus Fragment of Mutated Huntingtin

Author

Benchoua, Alexandra, primary, Trioulier, Yaël, additional, Zala, Diana, additional, Gaillard, Marie-Claude, additional, Lefort, Nathalie, additional, Dufour, Noelle, additional, Saudou, Frederic, additional, Elalouf, Jean-Marc, additional, Hirsch, Etienne, additional, Hantraye, Philippe, additional, Déglon, Nicole, additional, and Brouillet, Emmanuel, additional

Published
2006
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39. Short exposure to Notch ligand Delta-4 is sufficient to induce T-cell differentiation program and to increase the T cell potential of primary human CD34+ cells

Author

Lefort, Nathalie, Benne, Clarisse, Lelièvre, Jean Daniel, Dorival, Céline, Balbo, Michèle, Sakano, Seiji, Coulombel, Laure, and Lévy, Yves

Subjects
*CELL differentiation, *CORD blood, *GENETIC transcription, *LYMPHOCYTES
Abstract

Objective: The Notch pathway plays a key role in cell fate choices and in T-cell development. The goal of our study was to evaluate whether a short in vitro stimulation of the Notch pathway may alter human progenitor cell behavior. Methods: CD34+ cord blood progenitors were exposed for 4 days to either immobilized Notch ligand Delta-4 or in control conditions. Phenotypic and molecular changes induced by the short stimulation were assessed at day 4. Next, long-term alteration of the fate of these progenitors was assessed in culture conditions suitable for B (coculture with MS5 stromal cells) and T (FTOC and OP9 stromal cells expressing Delta-4 systems) cell differentiation. Results: Notch activation was sufficient to trigger immunophenotypic and molecular changes consistent with early T-cell lineage differentiation. Delta-4 induced, in 4 days, CD7+cytCD3ɛ+ cells. This paralleled at the gene-transcription level with de novo expression of several T cell–related transcription factors and TCRγ rearrangement, while B cell transcripts were simultaneous silenced. As compared to non-Delta-4 primed cells, these early changes translated to long-term alteration of the potential of cells. Delta-4 priming led to an acceleration of T-cell development, including a completion of the TCR rearrangement, when cells were cultured in systems suitable for T-cell development while B-cell development was inhibited. Conclusion: A transient Notch activation is sufficient to promote T-cell differentiation from cord blood CD34+ cells. This system may be a useful tool for the amplification and the quantification of the T potential of CD34+ cells in various disease conditions. [Copyright &y& Elsevier]

Published
2006
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40. Generation of an iPSC line (IMAGINi011-A) from a patient carrying a STING mutation.

Author

Barnabei L, Castela M, Banal C, Lefort N, and Rieux-Laucat F

Abstract

Mutation in STING1gene, which encodes stimulator of type I IFN gene (STING) leads to its constitutive activation and thereby to a severe vasculopathy and sometimes a lupus-like disease. We generated induced pluripotent stem cells (iPSCs) from a patient carrying a rare heterozygous variant c.463G > A (resulting in a p.V155M substitution) in STING1. Cells from this patient, which were reprogrammed by non-integrative viral transduction, had normal karyotype, expressed pluripotency markers and were able to differentiate into the three germ cell layers., (Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.)

Published
2020
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41. High N-glycan multiplicity is critical for neuronal adhesion and sensitizes the developing cerebellum to N-glycosylation defect.

Author

Medina-Cano D, Ucuncu E, Nguyen LS, Nicouleau M, Lipecka J, Bizot JC, Thiel C, Foulquier F, Lefort N, Faivre-Sarrailh C, Colleaux L, Guerrera IC, and Cantagrel V

Subjects
3-Oxo-5-alpha-Steroid 4-Dehydrogenase deficiency, 3-Oxo-5-alpha-Steroid 4-Dehydrogenase metabolism, Animals, Axon Guidance, Cell Adhesion, Cell Adhesion Molecules metabolism, Cell Differentiation, Cell Membrane metabolism, Cerebellum embryology, Cytoplasmic Granules metabolism, Gene Deletion, Glycosylation, Immunoglobulins metabolism, Induced Pluripotent Stem Cells metabolism, Membrane Proteins deficiency, Membrane Proteins metabolism, Mice, Knockout, Motor Activity, Mutation genetics, Neural Pathways metabolism, Proteomics, Purkinje Cells metabolism, Reproducibility of Results, Unfolded Protein Response, Cerebellum metabolism, Neurons cytology, Neurons metabolism, Polysaccharides metabolism
Abstract

Proper brain development relies highly on protein N-glycosylation to sustain neuronal migration, axon guidance and synaptic physiology. Impairing the N-glycosylation pathway at early steps produces broad neurological symptoms identified in congenital disorders of glycosylation. However, little is known about the molecular mechanisms underlying these defects. We generated a cerebellum specific knockout mouse for Srd5a3 , a gene involved in the initiation of N-glycosylation. In addition to motor coordination defects and abnormal granule cell development, Srd5a3 deletion causes mild N-glycosylation impairment without significantly altering ER homeostasis. Using proteomic approaches, we identified that Srd5a3 loss affects a subset of glycoproteins with high N-glycans multiplicity per protein and decreased protein abundance or N-glycosylation level. As IgSF-CAM adhesion proteins are critical for neuron adhesion and highly N-glycosylated, we observed impaired IgSF-CAM-mediated neurite outgrowth and axon guidance in Srd5a3 mutant cerebellum. Our results link high N-glycan multiplicity to fine-tuned neural cell adhesion during mammalian brain development., Competing Interests: DM, EU, LN, MN, JL, JB, CT, FF, NL, CF, LC, IG, VC No competing interests declared, (© 2018, Medina-Cano et al.)

Published
2018
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42. [Jumping translocations of chromosome 1q are recurring chromosomal -aberrations in neural derivatives of pluripotent stem cells].

Author

Varela C, Denis JA, Peschanski M, and Lefort N

Subjects
Cell Differentiation genetics, DNA Transposable Elements genetics, DNA Transposable Elements physiology, Genomic Instability, Humans, Neurons cytology, Neurons metabolism, Pluripotent Stem Cells metabolism, Recurrence, Time Factors, Chromosome Aberrations statistics & numerical data, Chromosomes, Human, Pair 1 genetics, Neurons physiology, Pluripotent Stem Cells physiology, Translocation, Genetic genetics
Published
2012
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43. [A recurrent hotspot of genomic instability identified in human ES cells].

Author

Lefort N, Feyeux M, Bas C, Féraud O, Bennaceur-Griscelli A, Tachdjian G, Peschanski M, and L Perrier A

Subjects
Cell Division, Cell Transformation, Neoplastic, Chromosome Aberrations embryology, Chromosome Aberrations statistics & numerical data, Embryonic Stem Cells cytology, Humans, Karyotyping, Membrane Proteins, Receptors, Steroid, Saccharomyces cerevisiae Proteins, Embryonic Stem Cells physiology, Genomic Instability
Published
2009
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44. Association of a common coding polymorphism (N453S) of the cytochrome P450 1B1 (CYP1B1) gene with optic disc cupping and visual field alteration in French patients with primary open-angle glaucoma.

Author

Melki R, Lefort N, Brézin AP, and Garchon HJ

Subjects
Alleles, Aryl Hydrocarbon Hydroxylases, Cytochrome P-450 CYP1B1, France epidemiology, Genotype, Glaucoma, Open-Angle ethnology, Humans, Intraocular Pressure, Polymerase Chain Reaction, Visual Field Tests, Cytochrome P-450 Enzyme System genetics, Glaucoma, Open-Angle genetics, Optic Disk pathology, Optic Nerve Diseases genetics, Polymorphism, Single Nucleotide, Vision Disorders genetics, Visual Fields
Abstract

Purpose: To investigate a role of common polymorphisms of the CYP1B1 gene in French patients with primary open-angle glaucoma (POAG)., Methods: Six common CYP1B1 variants, 5 coding and one in promoter, were compared in 224 unrelated French Caucasian POAG patients, excluding those with a CYP1B1 mutation, and in 47 population-matched controls with a normal ophthalmic examination. Allelic associations were assessed with the D' and r2 parameters. An effect of the representative variants on subphenotypes, including the age and the intraocular pressure at diagnosis, the cup to disk ratio, and the visual field alteration, was tested by multivariate analyses., Results: Allele and haplotype frequencies were similar in patients and in controls. Five variants formed two groups with tightly correlated alleles while the sixth one, N453S, was independent. The age and the intraocular pressure at diagnosis were not influenced by any of the variants. In contrast, the 453*Serine allele was associated with decreased cupping of the optic disk (Odds ratio=0.32, 95% CI: 0.15-0.70; p=0.0036) and with a milder alteration of the visual field (p=0.025)., Conclusions: The common N453S coding variant of CYP1B1 is potentially a factor of severity in POAG patients.

Published
2005

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