Search

Your search keyword '"Duchenne Parent Project"' showing total 5 results
Start Over Author "Duchenne Parent Project" Topic 0301 basic medicine
5 results on '"Duchenne Parent Project"'

1. Delivery of oligonucleotide‐based therapeutics: challenges and opportunities

Author

Annemieke Aartsma-Rus, Marisol Montolio, Gisela Gaina, Camilla Foged, Suzan M. Hammond, Alejandro Garanto, David R. Jones, Lourdes R. Desviat, Giuseppina Covello, Sabine Krause, Magdalena Guzowska, Virginia Arechavala-Gomeza, Sven Even F. Borgos, Willeke M. C. van Roon-Mom, Taavi Lehto, Sandra Alves, Ronald A.M. Buijsen, Michela A. Denti, Aurélie Goyenvalle, Rob W.J. Collin, Irina Holodnuka, Lucia Echevarria, Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), DFF-4184-00422 20577, 446002002 Foundation Fighting Blindness, FFB: PPA-0517-0717-RAD Fundación Ramón Areces Horizon 2020 Framework Programme, H2020: 721058, 761104 Muscular Dystrophy UK, MDUK Medical Research Council, MRC Institut National de la Santé et de la Recherche Médicale, Inserm Eesti Teadusagentuur, ETAg: PSG226 Ikerbasque, Basque Foundation for Science Prinses Beatrix Spierfonds Instituto de Salud Carlos III, ISCIII: CPII17/00004 Ministerio de Ciencia e Innovación, MICINN: PID2019-105344RB-I00 Duchenne Parent Project Hersenstichting: DR-2018-00253 Friedrich-Baur-Stiftung European Regional Development Fund, ERDF Algemene Nederlandse Vereniging ter voorkoming van Blindheid, ANVVB Landelijke Stichting voor Blinden en Slechtzienden, LSBS Stichting Retina Fonds: 2015-31, 2018-21 Stichting Blinden-Penning Ministerul Cercetării şi Inovării, MCI: 31N/2016/PN 16.22.02.05, PTDC/BBB-BMD/6301/2014, This work was supported by funding from Cooperation of Science and Technology (COST) Action CA17103 (networking grant to V.A-G). V.A-G holds a Miguel Servet Fellowship from the ISCIII [grant reference CPII17/00004] that is part-funded by the European Regional Development Fund (ERDF/FEDER) and also acknowledges funding from Ikerbasque (Basque Foundation for Science). S.M.H is funded by the Medical Research Council and Muscular Dystrophy UK. A.A-R receives funding from amongst others the Duchenne Parent Project, Spieren voor Spieren, the Prinses Beatrix Spierfonds, Duchenne UK and through Horizon2020 project BIND. A.G and R.W.J.C are supported by several foundations including the Algemene Nederlandse Vereniging ter Voorkoming van Blindheid, Stichting Blinden-Penning, Landelijke Stichting voor Blinden en Slechtzienden, Stichting Oogfonds Nederland, Stichting Macula Degeneratie Fonds, and Stichting Retina Nederland Fonds (who contributed through UitZicht 2015-31 and 2018-21), together with the Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp, Stichting tot Verbetering van het Lot der Blinden, Stichting voor Ooglijders, and Stichting Dowilvo, as well as the Foundation Fighting Blindness USA, grant no. PPA-0517-0717-RAD. R.A.M.B is supported by Hersenstichting Nederland Grant DR-2018-00253. G.G. is supported by Ministry of Research and Innovation in Romania/National Program 31N/2016/PN 16.22.02.05. S.A is supported by Project PTDC/BBB-BMD/6301/2014 (Funda??o para a Ci?ncia e a Tecnologia?MCTES, Portugal). L.R.D. is supported by Fundaci?n Ram?n Areces Grant XVII CN and Spanish Ministry of Science and Innovation (MICINN, grant PID2019-105344RB-I00). T.L is supported by Estonian Research Council grant PSG226. S.K is supported by the Friedrich-Baur-Stiftung. C.F is funded by The Danish Council for Independent Research, Technology and Production Sciences (grant number DFF-4184-00422). W.vRM is supported by ZonMw Programme Translational Research 2 [Project number 446002002], Campaign Team Huntington and AFM Telethon [Project number 20577]. S.E.B is supported by the H2020 projects B-SMART, Grant number 721058, and REFINE, Grant number 761104. A.T.G is supported by the Institut National de la sant? et la recherche m?dicale (INSERM) and the Association Monegasque contre les myopathies (AMM). L.E. is founded by the Association Monegasque contre les myopathies (AMM)., UAM. Departamento de Biología Molecular, Ministerio de Ciencia y Tecnología (España), Instituto de Salud Carlos III, Ikerbasque Basque Foundation for Science, Medical Research Council (UK), Duchenne UK, Foundation Fighting Blindness, Netherlands Brain Foundation, Ministerio de Ciencia e Innovación (España), Fundação para a Ciência e a Tecnologia (Portugal), and Fundación Ramón Areces

Subjects
safety, 0301 basic medicine, Medicine (General), Computer science, [SDV]Life Sciences [q-bio], Aptamer, Gene Expression, Review, Computational biology, QH426-470, Small Interfering, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], 03 medical and health sciences, R5-920, 0302 clinical medicine, Chemical Biology, Marketed products, Genetics, Cost of goods, Antisense, RNA, Small Interfering, Genetica Humana, Antisense Oligonucleotides, oligonucleotides, Oligonucleotide, RNA therapeutics, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Oligonucleotides, Antisense, Biología y Biomedicina / Biología, RNA Biology, preclinical models, Doenças Genéticas, 3. Good health, 030104 developmental biology, delivery, Nanoparticles, Oligonucleotides, Antisense oligonucleotides, RNA, Molecular Medicine, Synthetic Biology & Biotechnology, 030217 neurology & neurosurgery
Abstract

Nucleic acid‐based therapeutics that regulate gene expression have been developed towards clinical use at a steady pace for several decades, but in recent years the field has been accelerating. To date, there are 11 marketed products based on antisense oligonucleotides, aptamers and small interfering RNAs, and many others are in the pipeline for both academia and industry. A major technology trigger for this development has been progress in oligonucleotide chemistry to improve the drug properties and reduce cost of goods, but the main hurdle for the application to a wider range of disorders is delivery to target tissues. The adoption of delivery technologies, such as conjugates or nanoparticles, has been a game changer for many therapeutic indications, but many others are still awaiting their eureka moment. Here, we cover the variety of methods developed to deliver nucleic acid‐based therapeutics across biological barriers and the model systems used to test them. We discuss important safety considerations and regulatory requirements for synthetic oligonucleotide chemistries and the hurdles for translating laboratory breakthroughs to the clinic. Recent advances in the delivery of nucleic acid‐based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide‐based therapeutics., Recent advances in the delivery of nucleic acid‐based therapeutics and in the development of model systems, as well as safety considerations and regulatory requirements for synthetic oligonucleotide chemistries are discussed in this review on oligonucleotide‐based therapeutics.

Published
2021
Full Text
View/download PDF

2. The FibromiR miR-214-3p Is Upregulated in Duchenne Muscular Dystrophy and Promotes Differentiation of Human Fibro-Adipogenic Muscle Progenitors

Author

Claude J. Dechesne, Georges Vassaux, Julien Fassy, Virginie Magnone, Claudine Moratal, Nicolas Nottet, Noémie Clément, Nicolas Pottier, Pascal Peraldi, Nicole Arrighi, Romain Larrue, Kevin Lebrigand, Sandy Fellah, Bernard Mari, Christian Dani, Nicolas Pons, Grégoire Savary, Institut de Biologie Valrose (IBV), Université Nice Sophia Antipolis (... - 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), FHU OncoAge - Pathologies liées à l’âge [CHU Nice] (OncoAge), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 (CANTHER), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), This work was supported by funds from Institut National de la Santé et de la Recherche Médicale (Inserm), Centre National de la Recherche Scientifique (CNRS), the « Association Française contre les Myopathies, AFM (through grant HuMusmiR #17708 and a PhD fellowship for CM), the French Government (Agence Nationale de Recherche, ANR) ANR-PRCI FIBROMIR, the Investments for the Future LABEX SIGNALIFE (ANR-11-LABX-0028- 551 01), the Netherland Duchenne Parent Project and ITMO Cancer Aviesan (Alliance Nationale pour les Sciences de la Vie et de la Santé, National Alliance for Life Science and Health) within the framework of the Cancer Plan (Plan Cancer 2018 ARN non-codants en cancérologie: du fondamental au translationnel n° 18CN045)., ANR-18-CE92-0009,FIBROMIR,MicroARN et Interactions Epithélio-Mesenchymateuses dans les Pathologies Pulmonaires(2018), ANR-11-LABX-0028,SIGNALIFE,Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie(2011), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Pharmacologie Moléculaire et Cellulaire [UNIV Côte d'Azur] (UPMC)-Université Côte d'Azur (UCA), RUIZ, Caroline, APPEL À PROJETS GÉNÉRIQUE 2018 - MicroARN et Interactions Epithélio-Mesenchymateuses dans les Pathologies Pulmonaires - - FIBROMIR2018 - ANR-18-CE92-0009 - AAPG2018 - VALID, and Centres d'excellences - Réseau d'Innovation sur les Voies de Signalisation en Sciences de la Vie - - SIGNALIFE2011 - ANR-11-LABX-0028 - LABX - VALID

Subjects
0301 basic medicine, Male, Duchenne muscular dystrophy, Muscle Development, microRNA (miRNA), 0302 clinical medicine, Fibrosis, Adipocytes, Medicine, Biology (General), Child, Myofibroblasts, education.field_of_study, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Adipogenesis, Stem Cells, Cell Differentiation, General Medicine, Middle Aged, medicine.anatomical_structure, 030220 oncology & carcinogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], transforming growth factor beta (TGFβ), Female, Fibroblast Growth Factor 2, Myofibroblast, Signal Transduction, Adult, congenital, hereditary, and neonatal diseases and abnormalities, Adolescent, QH301-705.5, Population, Article, Transforming Growth Factor beta1, 03 medical and health sciences, Downregulation and upregulation, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], microRNA, Humans, Receptor, Fibroblast Growth Factor, Type 1, Progenitor cell, education, Muscle, Skeletal, Base Sequence, business.industry, Gene Expression Profiling, fibrosis, Skeletal muscle, medicine.disease, fibro-adipogenic progenitor (FAP), Muscular Dystrophy, Duchenne, MicroRNAs, 030104 developmental biology, FGFR1, Gene Expression Regulation, Duchenne muscular dystrophy (DMD), Cancer research, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Fibrosis is a deleterious invasion of tissues associated with many pathological conditions, such as Duchenne muscular dystrophy (DMD) for which no cure is at present available for its prevention or its treatment. Fibro-adipogenic progenitors (FAPs) are resident cells in the human skeletal muscle and can differentiate into myofibroblasts, which represent the key cell population responsible for fibrosis. In this study, we delineated the pool of microRNAs (miRNAs) that are specifically modulated by TGFβ1 in FAPs versus myogenic progenitors (MPs) by a global miRNome analysis. A subset of candidates, including several “FibromiRs”, was found differentially expressed between FAPs and MPs and was also deregulated in DMD versus healthy biopsies. Among them, the expression of the TGFβ1-induced miR-199a~214 cluster was strongly correlated with the fibrotic score in DMD biopsies. Loss-of-function experiments in FAPs indicated that a miR-214-3p inhibitor efficiently blocked expression of fibrogenic markers in both basal conditions and following TGFβ1 stimulation. We found that FGFR1 is a functional target of miR-214-3p, preventing the signaling of the anti-fibrotic FGF2 pathway during FAP fibrogenesis. Overall, our work demonstrates that the « FibromiR » miR-214-3p is a key activator of FAP fibrogenesis by modulating the FGF2/FGFR1/TGFβ axis, opening new avenues for the treatment of DMD.

Published
2021
Full Text
View/download PDF

3. Aldehyde dehydrogenases contribute to skeletal muscle homeostasis in healthy, aging, and Duchenne muscular dystrophy patients

Author

Cyril Catelain, Stéphane Blot, Pierre Joanne, Jean-Thomas Vilquin, Onnik Agbulut, Jessy Etienne, Isabel Punzón, Stéphanie Riveron, Jérémy Lafable, Alexandra Clarissa Bayer, Centre de recherche en myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), This work was supported by the DIM-STEMPOLE from Région Ile-de-France(J.E.),theAssociationFrançaisecontrelesMyopathies (AFM, C.C., S.R., and J.L.), and by grants from the Duchenne Parent Project from the Netherlands (DPP), from the Ligue contre la Cardiomyopathie, and from the Agence de Biomédecine., Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM), California Institute for Quantitative Biosciences [Berkeley] (QB3-Berkeley), University of California [Berkeley], University of California-University of California, Institut de Biologie Paris Seine (IBPS), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Myologie, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Vilquin, Jean-Thomas, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Duchenne muscular dystrophy, medicine.medical_specialty, Cell type, Aging, lcsh:Diseases of the musculoskeletal system, [SDV]Life Sciences [q-bio], Aldehyde dehydrogenase, Dog model, Skeletal muscle, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], lcsh:QM1-695, 03 medical and health sciences, 0302 clinical medicine, Physiology (medical), Internal medicine, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Myocyte, Orthopedics and Sports Medicine, Non‐human primate, ComputingMilieux_MISCELLANEOUS, biology, business.industry, lcsh:Human anatomy, Original Articles, medicine.disease, Non-human primate, [SDV] Life Sciences [q-bio], ALDH1A1, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Myogenic, 030220 oncology & carcinogenesis, biology.protein, CD146, Original Article, lcsh:RC925-935, Stem cell, business, Human
Abstract

International audience; BACKGROUND:Aldehyde dehydrogenases (ALDHs) are key players in cell survival, protection, and differentiation via the metabolism and detoxification of aldehydes. ALDH activity is also a marker of stem cells. The skeletal muscle contains populations of ALDH-positive cells amenable to use in cell therapy, whose distribution, persistence in aging, and modifications in myopathic context have not been investigated yet.METHODS:The Aldefluor® (ALDEF) reagent was used to assess the ALDH activity of muscle cell populations, whose phenotypic characterizations were deepened by flow cytometry. The nature of ALDH isoenzymes expressed by the muscle cell populations was identified in complementary ways by flow cytometry, immunohistology, and real-time PCR ex vivo and in vitro. These populations were compared in healthy, aging, or Duchenne muscular dystrophy (DMD) patients, healthy non-human primates, and Golden Retriever dogs (healthy vs. muscular dystrophic model, Golden retriever muscular dystrophy [GRMD]).RESULTS:ALDEF+ cells persisted through muscle aging in humans and were equally represented in several anatomical localizations in healthy non-human primates. ALDEF+ cells were increased in dystrophic individuals in humans (nine patients with DMD vs. five controls: 14.9 ± 1.63% vs. 3.6 ± 0.39%, P = 0.0002) and dogs (three GRMD dogs vs. three controls: 10.9 ± 2.54% vs. 3.7 ± 0.45%, P = 0.049). In DMD patients, such increase was due to the adipogenic ALDEF+ /CD34+ populations (11.74 ± 1.5 vs. 2.8 ± 0.4, P = 0.0003), while in GRMD dogs, it was due to the myogenic ALDEF+ /CD34- cells (3.6 ± 0.6% vs. 1.03 ± 0.23%, P = 0.0165). Phenotypic characterization associated the ALDEF+ /CD34- cells with CD9, CD36, CD49a, CD49c, CD49f, CD106, CD146, and CD184, some being associated with myogenic capacities. Cytological and histological analyses distinguished several ALDH isoenzymes (ALDH1A1, 1A2, 1A3, 1B1, 1L1, 2, 3A1, 3A2, 3B1, 3B2, 4A1, 7A1, 8A1, and 9A1) expressed by different cell populations in the skeletal muscle tissue belonging to multinucleated fibres, or myogenic, endothelial, interstitial, and neural lineages, designing them as potential new markers of cell type or of metabolic activity. Important modifications were noted in isoenzyme expression between healthy and DMD muscle tissues. The level of gene expression of some isoenzymes (ALDH1A1, 1A3, 1B1, 2, 3A2, 7A1, 8A1, and 9A1) suggested their specific involvement in muscle stability or regeneration in situ or in vitro.CONCLUSIONS:This study unveils the importance of the ALDH family of isoenzymes in the skeletal muscle physiology and homeostasis, suggesting their roles in tissue remodelling in the context of muscular dystrophies.

Published
2020
Full Text
View/download PDF

4. Delivery is key: lessons learnt from developing splice-switching antisense therapies

Author

Michela A. Denti, Samir El Andaloussi, Gisela Nogales-Gadea, Lourdes R. Desviat, Virginia Arechavala-Gomeza, Willeke M. C. van Roon-Mom, Bernard Khoo, Bård Smedsrød, Rayan Anwar, Caroline Godfrey, Taavi Lehto, Valentina Sardone, Stéphanie Lorain, Annemieke Aartsma-Rus, Aurélie Goyenvalle, Camilla Brolin, Petra Disterer, Telethon Italia, Duchenne Parent Project, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (España), Association Française contre les Myopathies, Fundación Ramón Areces, and European Commission

Subjects
0301 basic medicine, government.form_of_government, RNA Splicing, Drug Evaluation, Preclinical, Reviews, RNA therapy, Review, Pre-clinical models, Bioinformatics, Genetic therapy, 03 medical and health sciences, Drug Delivery Systems, Splice switching, Medicine, Animals, Humans, Pharmacology & Drug Discovery, Antisense therapy, 9. Industry and infrastructure, business.industry, Drug Administration Routes, Antisense oligonucleotides, Delivery, Toxicity, Molecular Medicine, toxicity, Genetic Therapy, VDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710::Medical microbiology: 715, Oligonucleotides, Antisense, 3. Good health, Variety (cybernetics), Clinical trial, pre‐clinical models, 030104 developmental biology, Risk analysis (engineering), VDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk mikrobiologi: 715, Key (cryptography), government, antisense oligonucleotides, delivery, business, pre-clinical models
Abstract

The use of splice-switching antisense therapy is highly promising, with a wealth of pre-clinical data and numerous clinical trials ongoing. Nevertheless, its potential to treat a variety of disorders has yet to be realized. The main obstacle impeding the clinical translation of this approach is the relatively poor delivery of antisense oligonucleotides to target tissues after systemic delivery. We are a group of researchers closely involved in the development of these therapies and would like to communicate our discussions concerning the validity of standard methodologies currently used in their pre-clinical development, the gaps in current knowledge and the pertinent challenges facing the field. We therefore make recommendations in order to focus future research efforts and facilitate a wider application of therapeutic antisense oligonucleotides., Fundación Ramón Areces and from Spanish Ministry of Economy and Competitiveness and European Regional Development Fund [grant reference SAF2013-43005-R]. B.S. was supported by a grant from the Tromsø Research Foundation. F.P.R. was supported by the Association Française contre les Myopathies (AFM-téléthon). M.A.D. was supported by Telethon Italia [grant reference GGP08244] and Italian Ministry of Health [grant reference GR-2008-1136933 and RF-2011-02347694]. S.L. was supported by The Dutch Duchenne Parent Project NL (DPP NL) and Association Française contre les Myopathies (AFM-téléthon). G.N.G. holds a Miguel Servet Fellowship from the ISCIII (grant reference CP14/00032] and a Fondo de Investigaciones Sanitarias Grant [grant reference PI15/01756], both are partfunded by the European Regional Development Fund (ERDF/FEDER). V.S. was supported by SKIP-NMD project, a European Community’s Seventh

Published
2017
Full Text
View/download PDF

5. Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functions via epigenetic modulation of Sca-1 and Pw1 promoters

Author

Frédéric Relaix, Marina Bouché, Francesco Fazi, Silvia Masciarelli, Giovanna Marazzi, Valeria Marrocco, Ilaria Iosue, Luca Madaro, Sonia Alonso-Martin, Piera Smeriglio, David Sassoon, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), French Ministry of Research ``Chaired Excellence', Muscular Dystrophy Association of America, Istituto Pasteur-Fondazione Cenci Bolognetti, Sapienza University of Rome, Duchenne Parent Project (Amsterdam, The Netherlands), European Community [Health-F5-2009-223098], ENDOSTEM (Activation of Vasculature Associated Stem Cells for the Repair and Maintenance of Muscle Tissue) [241440], Agence Nationale de la Recherche (Laboratoire d'Excellence Revive, Investissement d'Avenir) [ANR-10-LABX-73], IHU-ICAN projects, Italian Ministry for University and Research, Sapienza University of Rome, French Association against Myopathies (AFM), Telethon Italy, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
0301 basic medicine, Nude, Gene Expression, muscle cell fate, Biochemistry, Transgenic, Epigenesis, Genetic, Myoblasts, Mice, Myocyte, Antigens, Ly, Promoter Regions, Genetic, Cells, Cultured, Microscopy, muscle regeneration, Cultured, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Skeletal, 3. Good health, Cell biology, Chromatin, Muscle, Settore BIO/17 - ISTOLOGIA, Stem cell, Western, Biotechnology, Vanadium Compounds, cell reprogramming, muscle stem cells, PW1 interstitial cells, cell stemness, Cells, Myoblasts, Skeletal, Blotting, Western, Kruppel-Like Transcription Factors, Mice, Nude, Mice, Transgenic, Biology, Cell fate determination, Fluorescence, Interstitial cell, Cell Line, Promoter Regions, 03 medical and health sciences, Genetic, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Genetics, Animals, Regeneration, Antigens, Progenitor cell, Muscle, Skeletal, Cell reprogramming, Cell stemness, Muscle cell fate, Muscle regeneration, Membrane Proteins, Microscopy, Fluorescence, Muscle Cells, Protein Tyrosine Phosphatases, Molecular Biology, Transplantation, 030104 developmental biology, Ly, Cell culture, Epigenesis
Abstract

International audience; Understanding the regulation of the stem cell fate is fundamental for designing novel regenerative medicine strategies. Previous studies have suggested that pharmacological treatments with small molecules provide a robust and reversible regulation of the stem cell program. Previously, we showed that treatment with a vanadium compound influences muscle cell fate in vitro. In this study, we demonstrate that treatment with the phosphotyrosine phosphatase inhibitor bisperoxovanadium (BpV) drives primary muscle cells to a poised stem cell stage, with enhanced function in muscle regeneration in vivo following transplantation into injured muscles. Importantly, BpV-treated cells displayed increased self-renewal potential in vivo and replenished the niche in both satellite and interstitial cell compartments. Moreover, we found that BpV treatment induces specific activating chromatin modifications at the promoter regions of genes associated with stem cell fate, including Sca-1 and Pw1. Thus, our findings indicate that BpV resets the cell fate program by specific epigenetic regulations, such that the committed myogenic cell fate is redirected to an earlier progenitor cell fate stage, which leads to an enhanced regenerative stem cell potential.-Smeriglio, P., Alonso-Martin, S., Masciarelli, S., Madaro, L., Iosue, I., Marrocco, V., Relaix, F., Fazi, F., Marazzi, G., Sassoon, D. A., Bouche, M. Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functions via epigenetic modulation of Sca-1 and Pw1 promoters. FASEB J. 30, 1404-1415 (2016). www.fasebj.org

Published
2016
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results