title: Neonatal epicardial-derived progenitors aquire myogenic traits in skeletal muscle, but not cardiac muscle.
abstract: OBJECTIVE
  Epicardium-derived progenitor cells (EPDCs) differentiate into all heart cell types in the embryonic heart, yet their differentiation into cardiomyocytes in the adult heart is limited and poorly described. This may be due to EPDCs lacking myogenic potential or the inert adult heart missing regenerative signals essential for directed differentiation of EPDCs. Herein, we aimed to evaluate the myogenic potential of neonatal EPDCs in adult and neonatal mouse myocardium, as well as in skeletal muscle. The two latter tissues have an intrinsic capability to develop and regenerate, in contrast to the adult heart.
  
  
  METHODS
  Highly purified mouse EPDCs were transplanted into damaged neonatal and adult myocardium as well as regenerating skeletal muscle. Co-cultures with skeletal myoblasts were used to distinguish fusion independent myogenic conversion.
  
  
  RESULTS
  No donor EPDC-derived cardiomyocytes were observed in hearts. In contrast, a remarkable contribution of EPDCs to skeletal muscle myofiber formation was evident in vivo. Furthermore, co-cultures of EPDCs with myoblasts showed that EPDCs became part of multinucleated fibers and appeared to acquire myogenic traits independent of a fusion event. Fluorescence activated cell sorting of EPDCs co-cultured with and without myoblasts and subsequent qRT-PCR of 64 transcripts established that the myogenic phenotype conversion was accomplished through induction of a transcriptional myogenic program.
  
  
  CONCLUSIONS
  These results suggest that EPDCs may be more myogenic than previously anticipated. But, the heart may lack factors for induction of myogenesis of EPDCs, a scenario that should be taken into consideration when aiming for repair of damaged myocardium by stem cell transplantation.
authors: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark. Electronic address: dandersen@health.sdu.dk.
authors: Ditte C
authors: DC
authors: Andersen
authors: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors: Charlotte H
authors: CH
authors: Jensen
authors: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors: Ida
authors: I
authors: Skovrind
authors: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark; Clinical Institute, University of Southern Denmark, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors: Rikke Helin
authors: RH
authors: Johnsen
authors: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark; Cardiovascular and Renal Research, University of Southern Denmark, Winsloewparken 21(3rd), 5000 Odense, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors: Gunnhildur Asta
authors: GA
authors: Traustadottir
authors: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark; Cardiovascular and Renal Research, University of Southern Denmark, Winsloewparken 21(3rd), 5000 Odense, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors: Katrine S
authors: KS
authors: Aagaard
authors: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark; Cardiovascular and Renal Research, University of Southern Denmark, Winsloewparken 21(3rd), 5000 Odense, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors: Suganya
authors: S
authors: Ganesalingam
authors: Laboratory of Molecular and Cellular Cardiology, Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, Denmark; Cardiovascular and Renal Research, University of Southern Denmark, Winsloewparken 21(3rd), 5000 Odense, Denmark; The Danish Regenerative Center (danishcrm.com), Odense University Hospital, Sdr. Boulevard 29, 5000 Odense, Denmark.
authors: Søren P
authors: SP
authors: Sheikh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000166:cytology* / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000502:physiology; D010496:Pericardium / Q000166:cytology* / Q000502:physiology; D013234:Stem Cells / Q000502:physiology
keywords: Epicardial progenitors; Heart infarct; Mouse; Myogenic specification; Regenerating skeletal muscle; Stem cell transplantation