title: Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functions via epigenetic modulation of Sca-1 and Pw1 promoters.
abstract: 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 fatein 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 regenerationin vivofollowing transplantation into injured muscles. Importantly, BpV-treated cells displayed increased self-renewal potentialin vivoand 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, includingSca-1andPw1 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., Bouché, M. Phosphotyrosine phosphatase inhibitor bisperoxovanadium endows myogenic cells with enhanced muscle stem cell functionsviaepigenetic modulation of Sca-1 and Pw1 promoters.
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France.
authors.forename: Piera
authors.initials: P
authors.lastname: Smeriglio
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Alonso-Martin
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France.
authors.forename: Silvia
authors.initials: S
authors.lastname: Masciarelli
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France.
authors.forename: Luca
authors.initials: L
authors.lastname: Madaro
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France.
authors.forename: Ilaria
authors.initials: I
authors.lastname: Iosue
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France.
authors.forename: Valeria
authors.initials: V
authors.lastname: Marrocco
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Relaix
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France.
authors.forename: Francesco
authors.initials: F
authors.lastname: Fazi
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Marazzi
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France marina.bouche@uniroma1.it david.a.sassoon@gmail.com.
authors.forename: David A
authors.initials: DA
authors.lastname: Sassoon
authors.affiliation: *Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition Unité Mixte de Recherche en Santé 1166 INSERM/Sorbonne University (Pierre and Marie Curie University, Paris VI), Paris, France; Department of Anatomy, Histology, Forensic Medicine, and Orthopedics, Unit of Histology, Sapienza University of Rome, Rome, Italy; INSERM Unité 955 Institut Mondor de Recherche Biomédicale, Creteil, France; Université Paris-Est Créteil, Faculty of Medicine, Creteil, France; Sorbonne Universités, Pierre and Marie Curie University, Paris VI, INSERM Unité Mixte de Recherche en Santé 974, Centre National de la Recherche Scientifique FRE3617, Center for Research in Myology, Paris, France; Etablissement Français du Sang, Creteil, France; and Université Paris Est, Ecole Nationale Veterinaire d'Alfort, Maison Alfort, France marina.bouche@uniroma1.it david.a.sassoon@gmail.com.
authors.forename: Marina
authors.initials: M
authors.lastname: Bouché
mesh_terms: D000818:Animals; D000950:Antigens, Ly / Q000235:genetics*; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D044127:Epigenesis, Genetic; D015870:Gene Expression / Q000187:drug effects; D051741:Kruppel-Like Transcription Factors / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008819:Mice, Nude; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D017027:Protein Tyrosine Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017968:Vanadium Compounds / Q000494:pharmacology*
chemical_list: D000950:Antigens, Ly; D051741:Kruppel-Like Transcription Factors; C074650:Ly6a protein, mouse; D008565:Membrane Proteins; C097901:Peg3 protein, mouse; D017968:Vanadium Compounds; C472777:bisperoxovanadium; D017027:Protein Tyrosine Phosphatases
keywords: PW1 interstitial cells; cell reprogramming; cell stemness; muscle cell fate; muscle regeneration