EDUCATION AND TRAINING Degree Course of studies University year of achievement of the degree Master Degree Cellular Biology and Development

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1 TO MAGNIFICO RETTORE OF UNIVERSITA DEGLI STUDI DI MILANO Marielle Saclier CURRICULUM VITAE PERSONAL INFORMATION Surname Saclier Name Marielle Date of birth 08/08/1985 PRESENT OCCUPATION Appointment Postdoctoral Fellow Structure UNIVERSITY OF MILAN- LAB OF THE BIOLOGY DIFFERENTIATION FOR THERAPY- PROF. GRAZIELLA MESSINA EDUCATION AND TRAINING Degree Course of studies University year of achievement of the degree Master Degree Cellular Biology and Development University of Paris V Rene Descartes PhD Cellular Biology University of Paris V Rene Descartes REGISTRATION IN PROFESSIONAL ASSOCIATIONS Date of Association registration None City VIA FESTA DEL PERDONO, 7 C.A.P C.F TEL fax

2 FOREIGN LANGUAGES Languages English level of knowledge Written, spoken, read TRAINING OR RESEARCH ACTIVITY TRAINING ACTIVITIES Corso introduttivo alla sperimentazione animale, Istituto Mario Negri, Milan, Italy Animal experimentation level 1, Paris, France RESEARCH ACTIVITIES - Since 2014/07, Postdoctoral Fellow in the laboratory of Prof.ssa Graziella Messina, University of Milan, Department of Biosciences, Milan, Italy / /03 Ph.D Fellow in the laboratory of DR Benedicte Chazaud, Cochin Institut, Paris, France (6 months) Master 2 in the laboratory of Pr. Pierre-Paul Vidal, CeSeM, Paris, France PROJECT ACTIVITY Year today Project 1. Lacking of Nfix in Macrophages induces a defect of muscle regeneration through failed phenotypical switch Identification of macrophage subsets expressing Nfix during muscle regeneration upon acute injury by cell sorting and immunofluorescence. Role of Nfix in the acquisition of anti-inflammatory phenotype in vitro and in vivo. Evaluation of macrophages lacking Nfix trophic effect on myoblasts proliferation and differentiation in vitro. Characterization of muscle regeneration in mice lacking Nfix only in macrophages upon acute injury. 2. Silencing Nfix rescues muscular dystrophy by delaying muscle regeneration. Analysis of macrophages infiltration in Sgca null and Sgca null:nfix null mice during the progression of the myopathy. 3. Analyze of macrophage phenotype in Sgca null and Sgca null:nfix null mice during the progression of the myopathy. In vivo characterization of macrophages expressing Nfix in Sgca null mice by cell sorting and immunofluorescence. 4. Generation of LysM CRE :Nfix fl/fl :Sgca mouse (dystrophic mouse model deleted for Nfix in MPs) to verify at what extend and in which proportion the rescued phenotype observed in the Sgca null:nfix null dystrophic mice depends on lack of Nfix in satellite cells or macrophages. VIA FESTA DEL PERDONO, 7 C.A.P C.F TEL fax

3 2011/ /03 Università degli Studi, Laboratory of Prof.ssa Graziella Messina 1. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration. In vitro analysis of human macrophages trophic effect on human myoblasts proliferation, differentiation, migration and motility. Using specific blocking antibodies, identification of secreted molecules involved in the regulation of myogenesis by M1 and M2 macrophages in a human in vitro system. In vivo analysis of regenerating human muscle sections: correlation between pro- or anti-inflammatory macrophages and proliferating and differentiating myogenic cells. 2. Different macrophage subsets control matrix remodeling during skeletal muscle regeneration and fibrosis during degenerative myopathies. Phenotyping of macrophages in murine myopathic muscles during the progression of the disease by immunofluorescence (using pro-inflammatory and anti-inflammatory macrophages markers) and by qrt-pcr after cell sorting. Identification of the inflammatory state of macrophages in human Duchenne Muscular Dystrophy by immunofluorescence. Evaluation of the effect of each subset of macrophages (cell sorted) on fibroblasts proliferation, apoptosis and myofibroblasts differentiation, on ex-vivo coculture. Coculture of macrophages with WT or dystrophic myofibers to characterize effect of environment on macrophages polarization. Transplantation of sorted WT regenerative anti-inflammatory macrophages in dystrophic muscle to observed their effect on the progression of the disease. Evaluation of effect of anti-inflammatory molecule (H2S) injection in dystrophic mice on the progression of the disease. 3. CX3CR1 deficiency promotes muscle repair and rescues Ccl2-/- impaired regeneration by macrophage production of ApoE. In vitro analysis of WT, CX3CR1-/-, Ccl2-/- or CX3CR1:Ccl2-/- murine macrophages trophic effect on murine myoblasts proliferation and differentiation. 4. High Mobility Group Box 1 orchestrates tissue regeneration via CXCR4. Effect of 3S-HMGB1 or fr-hmgb1 on macrophage polarization in vitro. Evaluation of the macrophage infiltration after HMGB1 intra-muscular injection upon acute injury. Institut Cochin, Laboratory of DR Benericte Chazaud, mentor DR Benedicte Chazaud 2010 (6m) MyoD/NFATc2 interaction during myogenesis in mice. Investigation of the expression of the different isoforms of MyosinHeavyChain during the development of WT, MyoD (-/-),NFATc2 (-/-) and NFATc2 (-/-) MyoD (-/-) at E14,5 and E18,5. Mapping of NFATc2 and MyoD interaction by immunoprecipitation using NFATc2 and MyoD deletion constructs. CeSeM, laboratory of Pr. Pierre-Paul Vidal, Mentor Anne-Sophie Armand CONGRESSES AND SEMINARS Date Title Place 2017 Jun. Poster presentation Gordon Research Seminar and Conference, Advanced Mechanisms of Lucca (Barga), Italy. VIA FESTA DEL PERDONO, 7 C.A.P C.F TEL fax

4 Growth and Repair in Myogenesis, 2016 Jun. Poster presentation Society for Muscle Biology, Frontiers in Myogenesis, 2013 Nov. Poster presentation Myogenesis Symposium, Inflammation during degenerative myopathies Mar. Oral presentation Gc2iD Forum (Doctorale School) 2013 Feb. Oral presentation Ph.D Student day of Institut Cochin 2012 Nov. Oral presentation French Society of Myologie and Myogenesis Symposium 2012 Apr. Oral presentation Annual Endostem Meeting Pacific Grove, CA, USA. Montpellier, France. Rueil-Malmaison, France. Paris, France. Grenoble, France Barcelona, Spain PUBLICATIONS Articles in reviews Rossi Giuliana, Bonfanti Chiara, Antonini Stefania, Bastoni Mattia, Monteverde Stefania, Innocenzi Anna, Marielle Saclier, Valentina Taglietti and Messina Graziella. Silencing Nfix rescues muscular dystrophy by delaying muscle regeneration. (Nat Commun, 2017, in press). DOI: /s y. IF: 12,124 Saclier M*, Theret M*, Mounier R, Chazaud B. Effects of macrophage conditioned-medium on murine and human muscle cells analysis of proliferation, differentiation and fusion. Methods Mol Biol. 2017;1556: DOI: / _17. IF: 0,79 Ludovic Arnold*, Hélène Perrin*, Camille Baudesson de Chanville, Marielle Saclier, Patricia Hermand, Lucie Poupel, Elodie Guyon, Fabrice Licata, Wassila Carpentier, José Vilar, Rémi Mounier, Bénédicte Chazaud, Nora Benhabiles, Alexandre Boissonnas, Béhazine Combadiere and Christophe Combadiere. CX3CR1 deficiency promotes muscle repair and rescues Ccl2-/- impaired regeneration by macrophage production of ApoE. Nat Commun Dec 3;6:8972. DOI: /ncomms9972. IF : 12,124 Saclier M, Cuvellier S, Magnan M, Mounier R, Chazaud B. Monocyte/macrophage interactions with myogenic precursor cells during skeletal muscle regeneration. FEBS J Feb. 280(17): DOI: /febs IF: 3,902 Saclier M*, Yacoub-Youssef H*, Mackey AL, Arnold L, Ardjoune H, Magnan M, Sailhan F, Chelly J, Pavlath GK, Mounier R, Kjaer M, Chazaud B. Differentially activated macrophages orchestrate myogenic precursor cell fate during human skeletal muscle regeneration. Stem Cells 2013 Feb. 31(2): DOI: /stem IF: 5,599 VIA FESTA DEL PERDONO, 7 C.A.P C.F TEL fax

5 OTHER INFORMATION Tutor activity during thesis of on master 2 degree student during my Ph.D fellow and 2 during my PostDoc fellow Organization of JeCCo Symposium (JeCCo: Institut Cochin Young Reserchers Association). Program establishment, speakers and sponsors research, logistic in 2012 and 2013 Secretary of JeCCo (Institut Cochin Young Researchers Association) in 2012 to 2013 and Member of Sciences Promotion of JeCCo in 2011 to 2013 Declarations given in the present curriculum must be considered released according to art. 46 and 47 of DPR n. 445/2000. The present curriculum does not contain confidential and legal information according to art. 4, paragraph 1, points d) and e) of D.Lgs n Place and date: Milano, 21/09/2017 SIGNATURE VIA FESTA DEL PERDONO, 7 C.A.P C.F TEL fax

Supplementary Figure 1 Chemokine and chemokine receptor expression during muscle regeneration (a) Analysis of CR3CR1 mrna expression by real time-pcr

Supplementary Figure 1 Chemokine and chemokine receptor expression during muscle regeneration (a) Analysis of CR3CR1 mrna expression by real time-pcr at day 0, 1, 4, 10 and 21 post- muscle injury. (b)