Head: Capucine Trollet and Vincent Mouly
Our team is working on the molecular and cellular actors involved in human muscle regeneration, in muscle ageing and in muscular dystrophies including oculopharyngeal muscular dystrophy (OPMD) and Duchenne muscular dystrophy (DMD).
More precisely we are working on RNA metabolism, muscle regeneration, muscle stem cells, and fibrosis, with the final aim of developing innovative therapeutic approaches.
We have a strong expertise on human cellular models (this includes the immortalization facility that we have initiated) – and xenotransplantation (this includes several immunodeficient mouse models and grafting procedures).
Themes currently developed in parallel and in synergy
- Dissection of the molecular mechanisms relevant to OPMD and muscle ageing
- Dissection of cellular communication during muscle ageing, fibrosis and regeneration
- Development of therapeutic approaches.
Team members
Vincent Mouly (DR1 CNRS, co-team leader)
Capucine Trollet (DR2 INSERM, co-team leader)
Nami Altin (IE)
Mona Bensalah (IR)
Anne Bigot (CR AIM)
Alexis Boulinguiez (postdoc)
Gillian S Butler-Browne (DR1 INSERM, Emeritus)
Ludovic Gaut-Serey (postdoc)
Valentine Hanique (IE)
Samuel Horita (PhD student)
Jean Lacau St Guily (PUPH, Emeritus)
Kamel Mamchaoui (IR AIM)
Rose Mouigni (PhD student)
Laura Muraine (PhD)
Elisa Negroni (CR AIM)
Jessica Ohana (Engineer)
Contacts
vincent.mouly@upmc.fr
capucine.trollet@upmc.fr
MyoLine: a platform for the immortalization of human cells
Our team has demonstrated some important differences between man and mouse, in the regulation of the proliferation of myogenic precursors. We have chosen to work on human precursors, either in vitro or in vivo, in xenograft models that we have developed in successive European networks. Therefore, in collaboration with W. Wright, we have developed an approach for the immortalisation of human muscle precursors that allows them to retain their ability to differentiate: this has enabled the generation of immortal cell lines derived from patient cells.
This activity, developed with the full support of the AFM as well as the Dutch Duchenne Parent Project NL (DPP-NL) and the Jain Foundation, has resulted in the creation of a platform for the immortalisation of human cells.
This platform has generated over 85 different cell lines, from controls or pathological subjects. Over 20 different pathologies have been immortalised, some with several different mutations.
These cell lines are shared in collaboration with many international teams, either to study physiological or pathophysiological mechanisms, or to test innovative therapeutic approaches. Some of these cell lines have been shared with the pharmaceutical industry.
Figure legend: Examples of immortalised human myoblast cell lines in differentiation, including a DMD cell line suitable for exon skipping (DMD del 48-50)
Collaboration: France-Brazil International Associated Laboratory
Another specific aspect of our team is the development of international collaborations. In addition to numerous collaborations established over many years, we have set up an International Associated Laboratory between INSERM and Sorbonne University for France and FIOCRUZ and the Federal University of Rio de Janeiro for Brazil.
The IAL aims to synergise the expertise in muscle and neuromuscular diseases of French teams and the expertise in immunology and inflammation of the Brazilian teams.
The IAL has already been renewed once, has resulted in 14 publications and a common patent, as well as the exchange of three long-term post-docs, 5 jointly supervised PhDs and many short term exchanges, including visiting professorships in both countries. A common training component (masters and / or doctoral program) is being developed and will involve innovative Biotherapies in the muscle environment.
Figure legend: Human myoblasts in the damaged muscle of an immunodeficient mouse, identified by species-specific antibodies
Last publications
- Tone Y, Mamchaoui K, Tsoumpra MK, Hashimoto Y, Terada R, Maruyama R, Gait MJ, Arzumanov AA, McClorey G, Imamura M, Takeda S, Yokota T, Wood MJA, Mouly V, Aoki Y. Immortalized Canine Dystrophic Myoblast Cell Lines for Development of Peptide-Conjugated Splice-Switching Oligonucleotides. Nucleic Acid Ther. 2021 Apr;31(2):172-181. doi: 10.1089/nat.2020.0907.
- Cid-Díaz T, Leal-López S, Fernández-Barreiro F, González-Sánchez J, Santos-Zas I, Andrade-Bulos LJ, Rodríguez-Fuentes ME, Mosteiro CS, Mouly V, Casabiell X, Relova JL, Pazos Y, Camiña JP. Obestatin signalling counteracts glucocorticoid-induced skeletal muscle atrophy via NEDD4/KLF15 axis. J Cachexia Sarcopenia Muscle. 2021 Apr;12(2):493-505. doi: 10.1002/jcsm.12677.
- Saini J, Faroni A, Reid AJ, Mouly V, Butler-Browne G, Lightfoot AP, McPhee JS, Degens H, Al-Shanti N. Cross-talk between motor neurons and myotubes via endogenously secreted neural and muscular growth factors. Physiol Rep. 2021 Apr;9(8):e14791. doi: 10.14814/phy2.14791.
- Boyer O, Butler-Browne G, Chinoy H, Cossu G, Galli F, Lilleker JB, Magli A, Mouly V, Perlingeiro RCR, Previtali SC, Sampaolesi M, Smeets H, Schoewel-Wolf V, Spuler S, Torrente Y, Van Tienen F; Study Group (Negroni E). Myogenic Cell Transplantation in Genetic and Acquired Diseases of Skeletal Muscle. Front Genet. 2021 Aug 2;12:702547. doi:10.3389/fgene.2021.702547. eCollection 2021.PMID: 34408774
- Strings-Ufombah V, Malerba A, Kao SC, Harbaran S, Roth F, Cappellari O, Lu-Nguyen N, Takahashi K, Mukadam S, Kilfoil G, Kloth C, Roelvink P, Dickson G*, Trollet C*, Suhy D*. BB-301: a silence and replace AAV-based vector for the treatment of oculopharyngeal muscular dystrophy. Mol Ther Nucleic Acids. 2021 Feb 18;24:67-78. doi: 10.1016/j.omtn.2021.02.017. eCollection 2021 Jun 4.PMID: 33738139 (*co-last)
- Trollet C, Cheng AJ, Sylow L, Batista ML Jr, Pillon NJ. Editorial: Skeletal Muscle Immunometabolism. Front Physiol. 2021 Apr 28;12:683088. doi: 10.3389/fphys.2021.683088. eCollection 2021.PMID: 33995133
- Bamia A, Sinane M, Naït-Saïdi R, Dhiab J, Keruzoré M, Nguyen PH, Bertho A, Soubigou F, Halliez S, Blondel M, Trollet C, Simonelig M, Friocourt G, Béringue V, Bihel F, Voisset C. Anti-prion Drugs Targeting the Protein Folding Activity of the Ribosome Reduce PABPN1 Aggregation. Neurotherapeutics. 2021 Apr;18(2):1137-1150. doi: 10.1007/s13311-020-00992-6. Epub 2021 Feb 2.PMID: 33533011
- Trollet C, Boulinguiez A, Roth F, Stojkovic T, Butler-Browne G, Evangelista T, Lacau St Guily J, Richard P. Oculopharyngeal Muscular Dystrophy. 2001 Mar 8 [updated 2020 Oct 22]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021. PMID: 20301305
- Narici M, McPhee J, Conte M, Franchi MV, Mitchell K, Tagliaferri S, Monti E, Marcolin G, Atherton PJ, Smith K, Phillips B, Lund J, Franceschi C, Maggio M, Butler-Browne GS. Age-related alterations in muscle architecture are a signature of sarcopenia: the ultrasound sarcopenia index. J Cachexia Sarcopenia Muscle. 2021 Aug;12(4):973-982. doi: 10.1002/jcsm.12720. Epub 2021 Jun 1.PMID: 34060717
- Stocco A, Smolina N, Sabatelli P, Šileikytė J, Artusi E, Mouly V, Cohen M, Forte M, Schiavone M, Bernardi P. Treatment with a triazole inhibitor of the mitochondrial permeability transition pore fully corrects the pathology of sapje zebrafish lacking dystrophin. Pharmacol Res. 2021 Jan 8:105421. doi: 10.1016/j.phrs.2021.105421.
- Tiago T, Hummel B, Morelli FF, Basile V, Vinet J, Galli V, Mediani L, Antoniani F, Pomella S, Cassandri M, Garone MG, Silvestri B, Cimino M, Cenacchi G, Costa R, Mouly V, Poser I, Yeger-Lotem E, Rosa A, Alberti S, Rota R, Ben-Zvi A, Sawarkar R, Carra S. Small heat-shock protein HSPB3 promotes myogenesis by regulating the lamin B receptor. Cell Death Dis. 2021 May 6;12(5):452. doi: 10.1038/s41419-021-03737-1.
- Suárez-Calvet X, Fernández-Simón E, Piñol-Jurado P, Alonso-Pérez J, Carrasco-Rozas A, Lleixà C, López-Fernández S, Pons G, Soria L, Bigot A, Mouly V, Illa I, Gallardo E, Jaiswal JK, Díaz-Manera J.Isolation of human fibroadipogenic progenitors and satellite cells from frozen muscle biopsies. FASEB J. 2021 Sep;35(9):e21819. doi: 10.1096/fj.202100588R.PMID: 34405910
- Ebrahimi M, Lad H, Fusto A, Tiper Y, Datye A, Nguyen CT, Jacques E, Moyle LA, Nguyen T, Musgrave B, Chávez-Madero C, Bigot A, Chen C, Turner S, Stewart BA, Pegoraro E, Vitiello L, Gilbert PM. De novo revertant fiber formation and therapy testing in a 3D culture model of Duchenne muscular dystrophy skeletal muscle. Acta Biomater. 2021 Sep 15;132:227-244. doi: 10.1016/j.actbio.2021.05.020. Epub 2021 May 25.PMID: 34048976
- Gionet-Gonzales M, Casella A, Diloretto D, Ginnell C, Griffin KH, Bigot A, Leach JK. Sulfated Alginate Hydrogels Prolong the Therapeutic Potential of MSC Spheroids by Sequestering the Secretome. Adv Healthc Mater. 2021 Sep 5:e2101048. doi: 10.1002/adhm.202101048. Online ahead of print. PMID: 34486244
- Schmidt M, Weidemann A, Poser C, Bigot A, von Maltzahn J. Stimulation of Non-canonical NF-kappaB Through Lymphotoxin-beta-Receptor Impairs Myogenic Differentiation and Regeneration of Skeletal Muscle. Front Cell Dev Biol. 2021 Oct 5;9:721543. doi: 10.3389/fcell.2021.721543.
- Galli F, Mouly V, Butler-Browne G, Cossu G. Challenges in cell transplantation for muscular dystrophy. Exp Cell Res. 2021 Dec 1;409(1):112908. doi: 10.1016/j.yexcr.2021.112908. Epub 2021 Nov 1. PMID: 34736920 Review.
- Marchesi E, Bovolenta M, Preti L, Capobianco ML, Mamchaoui K, Bertoldo M, Perrone D. Synthesis and Exon-Skipping Properties of a 3′-Ursodeoxycholic Acid-Conjugated Oligonucleotide Targeting DMD Pre-mRNA: Pre-Synthetic versus Post-Synthetic Approach. Molecules. 2021 Dec 17;26(24):7662. doi: 10.3390/molecules26247662.PMID: 34946743
- Becker R, Vergarajauregui S, Billing F, Sharkova M, Lippolis E, Mamchaoui K, Ferrazzi F, Engel FB. Myogenin controls via AKAP6 non-centrosomal microtubule-organizing center formation at the nuclear envelope. Elife. 2021 Oct 4;10:e65672. doi: 10.7554/eLife.65672.PMID: 34605406
- Muraine L, Bensalah M, Dhiab J, Cordova G, Arandel L, Marhic A, Chapart M, Vasseur S, Benkhelifa-Ziyyat S, Bigot A, Butler-Browne G, Mouly V, Negroni E, Trollet C. Transduction Efficiency of Adeno-Associated Virus Serotypes After Local Injection in Mouse and Human Skeletal Muscle. Hum Gene Ther. 2020. Feb;31(3-4):233-240. doi: 10.1089/hum.2019.173. Epub 2020 Jan 24
- Bensalah M, Klein P, Riederer I, Chaouch S, Muraine L, Savino W, Butler-Browne GS, Trollet C, Mouly V, Bigot A, Negroni E. Combined methods to evaluate human cells in muscle xenografts. PLoS One. 2019 May 2;14(5):e0211522. doi: 10.1371/journal.pone.0211522. eCollection 2019.
- Malerba A, Roth F, Harish P, Dhiab J, Lu-Nguyen N, Cappellari O, Jarmin S, Mahoudeau A, Ythier V, Lainé J, Negroni E, Abgueguen E, Simonelig M, Guedat P, Mouly V, Butler-Browne G, Voisset C, Dickson G, Trollet C. Pharmacological modulation of the ER stress response ameliorates oculopharyngeal muscular dystrophy.Hum Mol Genet. 2019 May 15;28(10):1694-1708. doi: 10.1093/hmg/ddz007.
- Malerba A*, Klein P*, Bachtarzi H, Jarmin SA, Cordova G, Ferry A, Strings V, Espinoza MP, Mamchaoui K, Blumen SC, St Guily JL, Mouly V, Graham M, Butler-Browne G, Suhy DA, Trollet C**, Dickson G**. PABPN1 gene therapy for oculopharyngeal muscular dystrophy. Nat Commun. 2017 Mar 31;8:14848.
- Richard P*, Trollet C*, Stojkovic T, de Becdelievre A, Perie S, Pouget J, Eymard B; Neurologists of French Neuromuscular Reference Centers CORNEMUS and FILNEMUS. Correlation between PABPN1 genotype and disease severity in oculopharyngeal muscular dystrophy. Neurology. 2016 88(4):359-365.
- Klein P, Oloko M, Roth F, Montel V, Malerba A, Jarmin S, Gidaro T, Popplewell L, Perie S, Lacau St Guily J, de la Grange P, Antoniou MN, Dickson G, Butler-Browne G, Bastide B, Mouly V, Trollet C. Nuclear poly(A)-binding protein aggregates misplace a pre-mRNA outside of SC35 speckle causing its abnormal splicing. Nucleic Acids Res. 2016 Dec 15;44(22):10929-10945.
- Bigot A, Duddy WJ, Ouandaogo ZG, Negroni E, Mariot V, Ghimbovschi S, Harmon B, Wielgosik A, Loiseau C, Devaney J, Dumonceaux J, Butler-Browne G, Mouly V, Duguez S. Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle. Cell Rep. 2015 Nov 10;13(6):1172-1182. doi: 10.1016/j.celrep.2015.09.067.
- Chartier A, Klein P, Pierson S, Barbezier N, Gidaro T, Casas F, Carberry S, Dowling P, Maynadier L, Bellec M, Oloko M, Jardel C, Moritz B, Dickson G, Mouly V, Ohlendieck K, Butler-Browne G, Trollet C, Simonelig M. Mitochondrial dysfunction reveals the role of mRNA poly(a) tail regulation in oculopharyngeal muscular dystrophy pathogenesis. PLoS Genet. 2015 Mar 27;11(3):e1005092.
- Périé S, Trollet C, Mouly V, Vanneaux V, Mamchaoui K, Bouazza B, Pierre Marolleau J, Laforêt P, Chapon F, Eymard B, Butler-Browne G, Larghero J, St Guily JL. Autologous myoblast transplantation for oculopharyngeal muscular dystrophy: a Phase I/IIa clinical study. Mol Ther. 2014 Jan;22(1):219-25.
- Vallese D, Negroni E, Duguez S, Ferry A, Trollet C, Aamiri A, Vosshenirch CA, Füchtbauer EM, Di Santo JP, Vitiello L, Butler-Browne G, Mouly V. The Rag2-Il2rb-Dmd- mouse: a novel dystrophic and immunodeficient model to assess innovating therapeutic strategies for muscular dystrophies. Mol Ther. 2013.