Smeriglio Piera, Alonso-Martin Sonia, Masciarelli Silvia, Madaro Luca, Iosue Ilaria, Marrocco Valeria, Relaix Frédéric, Fazi Francesco, Marazzi Giovanna, Sassoon David A, Bouché Marina
*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.
*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
FASEB J. 2016 Apr;30(4):1404-15. doi: 10.1096/fj.15-275420. Epub 2015 Dec 15.
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.
了解干细胞命运的调控对于设计新型再生医学策略至关重要。先前的研究表明，小分子药物治疗可对干细胞程序进行强有力且可逆的调控。此前，我们发现钒化合物处理可在体外影响肌肉细胞命运。在本研究中，我们证明磷酸酪氨酸磷酸酶抑制剂双过氧钒（BpV）处理可使原代肌肉细胞进入一种处于准备状态的干细胞阶段，在移植到受损肌肉后，其在体内肌肉再生中的功能得到增强。重要的是，经BpV处理的细胞在体内显示出增加的自我更新潜力，并在卫星细胞和间质细胞区室中补充了生态位。此外，我们发现BpV处理可在与干细胞命运相关的基因（包括Sca-1和Pw1）的启动子区域诱导特定的激活染色质修饰。因此，我们的研究结果表明，BpV通过特定的表观遗传调控重置细胞命运程序，从而使已确定的成肌细胞命运重定向至更早的祖细胞命运阶段，进而导致再生干细胞潜力增强。-Smeriglio, P., Alonso-Martin, S., Masciarelli, S., Madaro, L., Iosue, I., Marrocco, V., Relaix, F., Fazi, F., Marazzi, G., Sassoon, D. A., Bouché, M. 磷酸酪氨酸磷酸酶抑制剂双过氧钒通过对Sca-1和Pw1启动子的表观遗传调控赋予成肌细胞增强的肌肉干细胞功能。
